View original ARBA rule on UniProt
Rule targeting ureohydrolase family proteins (arginase and agmatinase) involved in nitrogen metabolism and urea cycle, but critically lacking GO term annotations
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 has fundamental design flaws that make it unsuitable for GO annotation. The most critical issue is the complete absence of GO term annotations - the rule only provides pathway information. Additionally, it inappropriately groups functionally distinct enzymes (arginase and agmatinase) and has inconsistent taxonomic restrictions. While the biological pathway information is accurate, the lack of molecular function GO terms renders this rule useless for GO annotation purposes. This explains why it was flagged in the GO annotation issue tracker.
This rule should be deprecated because: (1) It provides no GO term annotations, only pathway information, making it unsuitable for GO annotation purposes; (2) It inappropriately conflates functionally distinct enzymes (arginase EC 3.5.3.1 vs agmatinase EC 3.5.3.11) that should have different molecular function annotations; (3) It has inconsistent and poorly justified taxonomic restrictions; (4) The broad condition set creates significant redundancy through nested subset relationships. A complete redesign would be needed to make this rule useful for GO annotation.
Rule has significant redundancy issues. Condition set 1 contains three nested InterPro terms where IPR014033 ⊆ IPR006035 ⊆ IPR023696, creating unnecessary complexity. The 8 condition sets target both related and unrelated enzymes, violating parsimony principles.
While the biochemical pathway information is well-supported, the rule fails to provide specific molecular function annotations that would be literature-supported. Arginase and agmatinase are well-characterized enzymes with distinct functions that should not be grouped under a single annotation rule.
Condition set 1 shows problematic nested subset relationships where all proteins with IPR014033 also have IPR006035 and IPR023696. All FunFam families are completely disjoint from each other but are subsets of the broader InterPro families, creating a complex overlap pattern that suggests poor rule design.
The rule provides NO GO terms whatsoever, only pathway information. This is completely inappropriate for GO annotation purposes. Proper molecular function terms should be GO:0004053 (arginase activity) for arginase and GO:0052689 (carboxylic acid dimethylamide hydrolase activity) for agmatinase.
The taxonomic restrictions are inconsistently applied and poorly justified. Some FunFams have no taxonomic restrictions while others are limited to specific lineages (Eukaryota, Viridiplantae, Fungi, Metazoa, Mammalia) without clear biological rationale. This creates an unnecessarily complex and potentially biased annotation pattern.
Rule provides no GO term annotations, only pathway information
Inappropriately groups functionally distinct enzymes (arginase vs agmatinase)
Contains significant condition overlap through nested InterPro subset relationships
Has inconsistent and poorly justified taxonomic restrictions
All FunFam families are completely disjoint from each other (0% overlap)
Condition set 1 shows nested subset relationships creating redundancy
22 subset relationships identified across 45 pairwise comparisons
id: ARBA00005098
description: 'Rule targeting ureohydrolase family proteins (arginase and agmatinase) involved in nitrogen metabolism and urea cycle, but critically lacking GO term annotations'
status: COMPLETE
rule_type: ARBA
rule:
rule_id: ARBA00005098
condition_sets:
- number: 1
conditions:
- condition_type: INTERPRO
value: IPR006035
curie: InterPro:IPR006035
label: Ureohydrolase
negated: false
- condition_type: INTERPRO
value: IPR014033
curie: InterPro:IPR014033
label: Arginase
negated: false
- condition_type: INTERPRO
value: IPR023696
curie: InterPro:IPR023696
label: Ureohydrolase domain superfamily
negated: false
notes: ''
pairwise_overlap:
- condition_a: IPR006035
condition_b: IPR014033
protein_database: SWISSPROT
count_a: 230
count_b: 41
intersection_count: 41
a_minus_b_count: 189
b_minus_a_count: 0
jaccard_similarity: 0.1782608695652174
containment_a_in_b: 0.1782608695652174
containment_b_in_a: 1.0
interpretation: SUBSET
- condition_a: IPR006035
condition_b: IPR023696
protein_database: SWISSPROT
count_a: 230
count_b: 334
intersection_count: 230
a_minus_b_count: 0
b_minus_a_count: 104
jaccard_similarity: 0.688622754491018
containment_a_in_b: 1.0
containment_b_in_a: 0.688622754491018
interpretation: SUBSET
- condition_a: IPR014033
condition_b: IPR023696
protein_database: SWISSPROT
count_a: 41
count_b: 334
intersection_count: 41
a_minus_b_count: 0
b_minus_a_count: 293
jaccard_similarity: 0.12275449101796407
containment_a_in_b: 1.0
containment_b_in_a: 0.12275449101796407
interpretation: SUBSET
- number: 2
conditions:
- condition_type: FUNFAM
value: 3.40.800.10:FF:000005
curie: CATH.FunFam:3.40.800.10:FF:000005
label: Arginase
negated: false
notes: ''
- number: 3
conditions:
- condition_type: FUNFAM
value: 3.40.800.10:FF:000008
curie: CATH.FunFam:3.40.800.10:FF:000008
label: Arginase
negated: false
- condition_type: TAXON
value: Eukaryota
curie: NCBITaxon:2759
label: Eukaryota
negated: false
notes: ''
- number: 4
conditions:
- condition_type: FUNFAM
value: 3.40.800.10:FF:000012
curie: CATH.FunFam:3.40.800.10:FF:000012
label: Arginase
negated: false
notes: ''
- number: 5
conditions:
- condition_type: FUNFAM
value: 3.40.800.10:FF:000007
curie: CATH.FunFam:3.40.800.10:FF:000007
label: Arginase 1, mitochondrial
negated: false
- condition_type: TAXON
value: Viridiplantae
curie: NCBITaxon:33090
label: Viridiplantae
negated: false
notes: ''
- number: 6
conditions:
- condition_type: FUNFAM
value: 3.40.800.10:FF:000009
curie: CATH.FunFam:3.40.800.10:FF:000009
label: Arginase
negated: false
- condition_type: TAXON
value: Fungi
curie: NCBITaxon:4751
label: Fungi
negated: false
notes: ''
- number: 7
conditions:
- condition_type: FUNFAM
value: 3.40.800.10:FF:000011
curie: CATH.FunFam:3.40.800.10:FF:000011
label: Arginase-1
negated: false
- condition_type: TAXON
value: Metazoa
curie: NCBITaxon:33208
label: Metazoa
negated: false
notes: ''
- number: 8
conditions:
- condition_type: FUNFAM
value: 3.40.800.10:FF:000002
curie: CATH.FunFam:3.40.800.10:FF:000002
label: Agmatinase
negated: false
- condition_type: TAXON
value: Mammalia
curie: NCBITaxon:40674
label: Mammalia
negated: false
notes: ''
go_annotations: []
reviewed_protein_count: 0
unreviewed_protein_count: 0
created_date: ''
modified_date: ''
entries:
- id: 3.40.800.10:FF:000002
type: FUNFAM
label: Agmatinase
appears_in_condition_sets:
- 8
protein_count: 5
related_entries:
- relationship: PREDICTS
target_id: IPR006035
containment: 0.022
jaccard_similarity: 0.022
intersection_count: 5
exclusive_count: 225
- relationship: EQUIV
target_id: IPR014033
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 5
- relationship: PREDICTS
target_id: IPR023696
containment: 0.015
jaccard_similarity: 0.015
intersection_count: 5
exclusive_count: 329
- relationship: EQUIV
target_id: 3.40.800.10:FF:000005
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 5
- relationship: EQUIV
target_id: 3.40.800.10:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 5
- relationship: EQUIV
target_id: 3.40.800.10:FF:000012
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 5
- relationship: EQUIV
target_id: 3.40.800.10:FF:000007
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 5
- relationship: EQUIV
target_id: 3.40.800.10:FF:000009
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 5
- relationship: EQUIV
target_id: 3.40.800.10:FF:000011
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 5
- id: 3.40.800.10:FF:000005
type: FUNFAM
label: Arginase
appears_in_condition_sets:
- 2
protein_count: 12
related_entries:
- relationship: PREDICTS
target_id: IPR006035
containment: 0.052
jaccard_similarity: 0.052
intersection_count: 12
exclusive_count: 218
- relationship: PREDICTS
target_id: IPR014033
containment: 0.293
jaccard_similarity: 0.293
intersection_count: 12
exclusive_count: 29
- relationship: PREDICTS
target_id: IPR023696
containment: 0.036
jaccard_similarity: 0.036
intersection_count: 12
exclusive_count: 322
- relationship: EQUIV
target_id: 3.40.800.10:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 12
- relationship: EQUIV
target_id: 3.40.800.10:FF:000012
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 12
- relationship: EQUIV
target_id: 3.40.800.10:FF:000007
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 12
- relationship: EQUIV
target_id: 3.40.800.10:FF:000009
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 12
- relationship: EQUIV
target_id: 3.40.800.10:FF:000011
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 12
- relationship: EQUIV
target_id: 3.40.800.10:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 12
- id: 3.40.800.10:FF:000007
type: FUNFAM
label: Arginase 1, mitochondrial
appears_in_condition_sets:
- 5
protein_count: 6
related_entries:
- relationship: PREDICTS
target_id: IPR006035
containment: 0.026
jaccard_similarity: 0.026
intersection_count: 6
exclusive_count: 224
- relationship: EQUIV
target_id: IPR014033
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: PREDICTS
target_id: IPR023696
containment: 0.018
jaccard_similarity: 0.018
intersection_count: 6
exclusive_count: 328
- relationship: EQUIV
target_id: 3.40.800.10:FF:000005
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000012
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000009
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000011
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- id: 3.40.800.10:FF:000008
type: FUNFAM
label: Arginase
appears_in_condition_sets:
- 3
protein_count: 8
related_entries:
- relationship: PREDICTS
target_id: IPR006035
containment: 0.035
jaccard_similarity: 0.035
intersection_count: 8
exclusive_count: 222
- relationship: PREDICTS
target_id: IPR014033
containment: 0.195
jaccard_similarity: 0.195
intersection_count: 8
exclusive_count: 33
- relationship: PREDICTS
target_id: IPR023696
containment: 0.024
jaccard_similarity: 0.024
intersection_count: 8
exclusive_count: 326
- relationship: EQUIV
target_id: 3.40.800.10:FF:000005
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000012
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000007
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000009
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000011
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- id: 3.40.800.10:FF:000009
type: FUNFAM
label: Arginase
appears_in_condition_sets:
- 6
protein_count: 6
related_entries:
- relationship: PREDICTS
target_id: IPR006035
containment: 0.026
jaccard_similarity: 0.026
intersection_count: 6
exclusive_count: 224
- relationship: PREDICTS
target_id: IPR014033
containment: 0.146
jaccard_similarity: 0.146
intersection_count: 6
exclusive_count: 35
- relationship: PREDICTS
target_id: IPR023696
containment: 0.018
jaccard_similarity: 0.018
intersection_count: 6
exclusive_count: 328
- relationship: EQUIV
target_id: 3.40.800.10:FF:000005
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000012
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000007
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000011
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- id: 3.40.800.10:FF:000011
type: FUNFAM
label: Arginase-1
appears_in_condition_sets:
- 7
protein_count: 6
related_entries:
- relationship: PREDICTS
target_id: IPR006035
containment: 0.026
jaccard_similarity: 0.026
intersection_count: 6
exclusive_count: 224
- relationship: PREDICTS
target_id: IPR014033
containment: 0.146
jaccard_similarity: 0.146
intersection_count: 6
exclusive_count: 35
- relationship: PREDICTS
target_id: IPR023696
containment: 0.018
jaccard_similarity: 0.018
intersection_count: 6
exclusive_count: 328
- relationship: EQUIV
target_id: 3.40.800.10:FF:000005
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000012
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000007
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000009
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- relationship: EQUIV
target_id: 3.40.800.10:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 6
- id: 3.40.800.10:FF:000012
type: FUNFAM
label: Arginase
appears_in_condition_sets:
- 4
protein_count: 8
related_entries:
- relationship: PREDICTS
target_id: IPR006035
containment: 0.035
jaccard_similarity: 0.035
intersection_count: 8
exclusive_count: 222
- relationship: PREDICTS
target_id: IPR014033
containment: 0.195
jaccard_similarity: 0.195
intersection_count: 8
exclusive_count: 33
- relationship: PREDICTS
target_id: IPR023696
containment: 0.024
jaccard_similarity: 0.024
intersection_count: 8
exclusive_count: 326
- relationship: EQUIV
target_id: 3.40.800.10:FF:000005
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000007
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000009
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000011
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- relationship: EQUIV
target_id: 3.40.800.10:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 8
- id: IPR006035
type: INTERPRO
label: Ureohydrolase
appears_in_condition_sets:
- 1
protein_count: 230
related_entries:
- relationship: PREDICTED_BY
target_id: IPR014033
containment: 1.0
jaccard_similarity: 0.178
intersection_count: 41
exclusive_count: 0
- relationship: PREDICTS
target_id: IPR023696
containment: 1.0
jaccard_similarity: 0.689
intersection_count: 230
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000005
containment: 1.0
jaccard_similarity: 0.052
intersection_count: 12
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000008
containment: 1.0
jaccard_similarity: 0.035
intersection_count: 8
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000012
containment: 1.0
jaccard_similarity: 0.035
intersection_count: 8
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000007
containment: 1.0
jaccard_similarity: 0.026
intersection_count: 6
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000009
containment: 1.0
jaccard_similarity: 0.026
intersection_count: 6
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000011
containment: 1.0
jaccard_similarity: 0.026
intersection_count: 6
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000002
containment: 1.0
jaccard_similarity: 0.022
intersection_count: 5
exclusive_count: 0
- id: IPR014033
type: INTERPRO
label: Arginase
appears_in_condition_sets:
- 1
protein_count: 41
related_entries:
- relationship: PREDICTS
target_id: IPR006035
containment: 0.178
jaccard_similarity: 0.178
intersection_count: 41
exclusive_count: 189
- relationship: PREDICTS
target_id: IPR023696
containment: 1.0
jaccard_similarity: 0.123
intersection_count: 41
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000005
containment: 1.0
jaccard_similarity: 0.293
intersection_count: 12
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000008
containment: 1.0
jaccard_similarity: 0.195
intersection_count: 8
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000012
containment: 1.0
jaccard_similarity: 0.195
intersection_count: 8
exclusive_count: 0
- relationship: EQUIV
target_id: 3.40.800.10:FF:000007
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 41
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000009
containment: 1.0
jaccard_similarity: 0.146
intersection_count: 6
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000011
containment: 1.0
jaccard_similarity: 0.146
intersection_count: 6
exclusive_count: 0
- relationship: EQUIV
target_id: 3.40.800.10:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 41
- id: IPR023696
type: INTERPRO
label: Ureohydrolase domain superfamily
appears_in_condition_sets:
- 1
protein_count: 334
related_entries:
- relationship: PREDICTED_BY
target_id: IPR006035
containment: 0.689
jaccard_similarity: 0.689
intersection_count: 230
exclusive_count: 104
- relationship: PREDICTED_BY
target_id: IPR014033
containment: 0.123
jaccard_similarity: 0.123
intersection_count: 41
exclusive_count: 293
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000005
containment: 1.0
jaccard_similarity: 0.036
intersection_count: 12
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000008
containment: 1.0
jaccard_similarity: 0.024
intersection_count: 8
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000012
containment: 1.0
jaccard_similarity: 0.024
intersection_count: 8
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000007
containment: 1.0
jaccard_similarity: 0.018
intersection_count: 6
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000009
containment: 1.0
jaccard_similarity: 0.018
intersection_count: 6
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000011
containment: 1.0
jaccard_similarity: 0.018
intersection_count: 6
exclusive_count: 0
- relationship: PREDICTED_BY
target_id: 3.40.800.10:FF:000002
containment: 1.0
jaccard_similarity: 0.015
intersection_count: 5
exclusive_count: 0
review_summary: 'This rule has fundamental design flaws that make it unsuitable for GO annotation. The most critical issue is the complete absence of GO term annotations - the rule only provides pathway information. Additionally, it inappropriately groups functionally distinct enzymes (arginase and agmatinase) and has inconsistent taxonomic restrictions. While the biological pathway information is accurate, the lack of molecular function GO terms renders this rule useless for GO annotation purposes. This explains why it was flagged in the GO annotation issue tracker.'
action: DEPRECATE
action_rationale: 'This rule should be deprecated because: (1) It provides no GO term annotations, only pathway information, making it unsuitable for GO annotation purposes; (2) It inappropriately conflates functionally distinct enzymes (arginase EC 3.5.3.1 vs agmatinase EC 3.5.3.11) that should have different molecular function annotations; (3) It has inconsistent and poorly justified taxonomic restrictions; (4) The broad condition set creates significant redundancy through nested subset relationships. A complete redesign would be needed to make this rule useful for GO annotation.'
suggested_modifications:
- 'Split into separate rules for arginase (EC 3.5.3.1) and agmatinase (EC 3.5.3.11)'
- 'Add appropriate GO molecular function terms: GO:0004053 (arginase activity) and GO:0052689 (carboxylic acid dimethylamide hydrolase activity) for agmatinase'
- 'Simplify condition sets by removing redundant InterPro hierarchies'
- 'Justify or remove taxonomic restrictions based on phylogenetic evidence'
- 'Add cellular component annotations where appropriate (mitochondrial vs cytosolic forms)'
parsimony:
assessment: OVERLY_COMPLEX
notes: 'Rule has significant redundancy issues. Condition set 1 contains three nested InterPro terms where IPR014033 ⊆ IPR006035 ⊆ IPR023696, creating unnecessary complexity. The 8 condition sets target both related and unrelated enzymes, violating parsimony principles.'
literature_support:
assessment: WEAK
notes: 'While the biochemical pathway information is well-supported, the rule fails to provide specific molecular function annotations that would be literature-supported. Arginase and agmatinase are well-characterized enzymes with distinct functions that should not be grouped under a single annotation rule.'
supported_by:
- reference_id: file:rules/arba/ARBA00005098/ARBA00005098-deep-research-manual.md
supporting_text: 'Arginase (EC 3.5.3.1): Converts L-arginine to L-ornithine + urea. Agmatinase (EC 3.5.3.11): Converts agmatine to putrescine + urea. Both enzymes belong to the ureohydrolase family and produce urea as a product, but have distinct substrates and biological roles.'
condition_overlap:
assessment: SIGNIFICANT
notes: 'Condition set 1 shows problematic nested subset relationships where all proteins with IPR014033 also have IPR006035 and IPR023696. All FunFam families are completely disjoint from each other but are subsets of the broader InterPro families, creating a complex overlap pattern that suggests poor rule design.'
supported_by:
- reference_id: file:rules/arba/ARBA00005098/ARBA00005098-analysis.yaml
supporting_text: 'IPR014033 is a complete subset of IPR006035 (100% containment). IPR006035 is a complete subset of IPR023696 (100% containment). This creates a hierarchical relationship: IPR014033 ⊆ IPR006035 ⊆ IPR023696.'
go_specificity:
assessment: MISMATCHED
notes: 'The rule provides NO GO terms whatsoever, only pathway information. This is completely inappropriate for GO annotation purposes. Proper molecular function terms should be GO:0004053 (arginase activity) for arginase and GO:0052689 (carboxylic acid dimethylamide hydrolase activity) for agmatinase.'
supported_by:
- reference_id: file:rules/arba/ARBA00005098/ARBA00005098.enriched.json
supporting_text: 'The rule contains only pathway annotation: Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine: step 1/1. No GO term annotations are present in the mainRule annotations section.'
taxonomic_scope:
assessment: UNNECESSARY
notes: 'The taxonomic restrictions are inconsistently applied and poorly justified. Some FunFams have no taxonomic restrictions while others are limited to specific lineages (Eukaryota, Viridiplantae, Fungi, Metazoa, Mammalia) without clear biological rationale. This creates an unnecessarily complex and potentially biased annotation pattern.'
supported_by:
- reference_id: file:rules/arba/ARBA00005098/ARBA00005098-deep-research-manual.md
supporting_text: 'Multiple CATH FunFam families with inconsistent taxonomic restrictions: Set 2 and 4 have no taxon restriction, while Sets 3,5,6,7,8 are restricted to different lineages without clear biological justification for the variation.'
confidence: 0.9
references:
- id: file:rules/arba/ARBA00005098/ARBA00005098-deep-research-manual.md
title: Manual deep research analysis
findings:
- statement: 'Rule provides no GO term annotations, only pathway information'
- statement: 'Inappropriately groups functionally distinct enzymes (arginase vs agmatinase)'
- statement: 'Contains significant condition overlap through nested InterPro subset relationships'
- statement: 'Has inconsistent and poorly justified taxonomic restrictions'
- id: file:rules/arba/ARBA00005098/ARBA00005098-analysis.yaml
title: Quantitative domain overlap analysis
findings:
- statement: 'All FunFam families are completely disjoint from each other (0% overlap)'
- statement: 'Condition set 1 shows nested subset relationships creating redundancy'
- statement: '22 subset relationships identified across 45 pairwise comparisons'
supported_by:
- reference_id: file:rules/arba/ARBA00005098/ARBA00005098-deep-research-manual.md
supporting_text: 'The most significant finding is that this rule provides NO GO term annotations, only pathway information. This is highly unusual for an ARBA rule and may be why this rule raised concerns in the GO annotation issue tracker.'