ARBA00005098

id: ARBA00005098
description: 'Assigns the pathway comment "Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine:
  step 1/1" (the arginase step) through nine alternative condition sets: InterPro arginase signatures in Chordata,
  a PANTHER subfamily in Bacteria, and seven CATH FunFams of superfamily 3.40.800.10, each with its own taxon.'
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00005098
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR006035
      curie: InterPro:IPR006035
      label: Ureohydrolase
      interpro_type: FAMILY
      negated: false
    - condition_type: INTERPRO
      value: IPR014033
      curie: InterPro:IPR014033
      label: Arginase
      interpro_type: FAMILY
      negated: false
    - condition_type: TAXON
      value: Chordata
      curie: NCBITaxon:7711
      label: Chordata
      negated: false
    notes: 'Swiss-Prot entries matching this set (2026-11-09): 16. 16 carry the PATHWAY comment "Nitrogen metabolism;
      urea cycle; L-ornithine and urea from L-arginine: step 1/1". UniProtKB entries matching: 1266.'
  - number: 2
    conditions:
    - condition_type: INTERPRO
      value: IPR020855
      curie: InterPro:IPR020855
      label: Ureohydrolase, manganese-binding site
      interpro_type: BINDING_SITE
      negated: false
    - condition_type: PANTHER
      value: PTHR43782:SF3
      curie: PANTHER:PTHR43782:SF3
      label: ARGINASE
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: false
    notes: 'Swiss-Prot entries matching this set (2026-11-09): 13. 13 carry the PATHWAY comment "Nitrogen metabolism;
      urea cycle; L-ornithine and urea from L-arginine: step 1/1". UniProtKB entries matching: 3432.'
  - number: 3
    conditions:
    - condition_type: FUNFAM
      value: 3.40.800.10:FF:000005
      curie: CATH.FunFam:3.40.800.10:FF:000005
      label: Arginase
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: false
    notes: 'Swiss-Prot entries matching this set (2026-11-09): 9. 9 carry the PATHWAY comment "Nitrogen metabolism;
      urea cycle; L-ornithine and urea from L-arginine: step 1/1". UniProtKB entries matching: 1028.'
  - number: 4
    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: 'Swiss-Prot entries matching this set (2026-11-09): 8. 8 carry the PATHWAY comment "Nitrogen metabolism;
      urea cycle; L-ornithine and urea from L-arginine: step 1/1". UniProtKB entries matching: 302.'
  - 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: 'Swiss-Prot entries matching this set (2026-11-09): 6. 6 carry the PATHWAY comment "Nitrogen metabolism;
      urea cycle; L-ornithine and urea from L-arginine: step 1/1". UniProtKB entries matching: 581.'
  - 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: 'Swiss-Prot entries matching this set (2026-11-09): 6. 6 carry the PATHWAY comment "Nitrogen metabolism;
      urea cycle; L-ornithine and urea from L-arginine: step 1/1". UniProtKB entries matching: 1028.'
  - 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: 'Swiss-Prot entries matching this set (2026-11-09): 6. 6 carry the PATHWAY comment "Nitrogen metabolism;
      urea cycle; L-ornithine and urea from L-arginine: step 1/1". UniProtKB entries matching: 195.'
  - number: 8
    conditions:
    - condition_type: FUNFAM
      value: 3.40.800.10:FF:000012
      curie: CATH.FunFam:3.40.800.10:FF:000012
      label: Arginase
      negated: false
    - condition_type: TAXON
      value: Pseudomonadati
      curie: NCBITaxon:3379134
      label: Pseudomonadati
      negated: false
    notes: 'Swiss-Prot entries matching this set (2026-11-09): 4. 4 carry the PATHWAY comment "Nitrogen metabolism;
      urea cycle; L-ornithine and urea from L-arginine: step 1/1". UniProtKB entries matching: 2143.'
  - number: 9
    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: 'Swiss-Prot entries matching this set (2026-11-09): 3. 3 carry the PATHWAY comment "Nitrogen metabolism;
      urea cycle; L-ornithine and urea from L-arginine: step 1/1". UniProtKB entries matching: 174.'
  go_annotations: []
  entries: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 6499
  created_date: '2020-05-12'
  modified_date: '2026-07-18'
  retrieved_date: '2026-11-09'
  source_condition_set_count: 9
review_summary: All nine live condition sets were checked against Swiss-Prot. Every reviewed match of every set
  carries the pathway comment (16, 13, 9, 8, 6, 6, 6, 4 and 3 entries for sets 1 to 9). Set 9 uses a FunFam whose
  CATH label is "Agmatinase", but its three mammalian Swiss-Prot members are AGMAT orthologues (human Q9BSE5, mouse
  A2AS89, rat Q0D2L3), which Swiss-Prot curates as guanidino acid hydrolase with arginase activity (EC 3.5.3.1,
  PubMed:36543883) and with this pathway comment. Checked against Swiss-Prot by UniProtKB query on 2026-11-09; TrEMBL
  matches were counted but not inspected.
action: ACCEPT
action_rationale: 'Every live condition set is supported by curated Swiss-Prot annotation: no reviewed match of
  any set lacks the pathway comment.'
taxonomic_scope:
  assessment: APPROPRIATE
  notes: Each set carries its own taxon condition (Chordata, Bacteria, Eukaryota, Viridiplantae, Fungi, Metazoa,
    Pseudomonadati, Mammalia), and within each the Swiss-Prot matches all carry the pathway comment.
annotation_assessments:
- annotation_kind: OTHER
  value: 'PATHWAY: Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine: step 1/1'
  assessment: CORRECT
  correct_examples:
  - P05089
  - P78540
  - P07824
  - Q9BSE5
  - Q0D2L3
  - A2AS89
  notes: 'Swiss-Prot matches with the pathway comment, by set: CS1 16/16, CS2 13/13, CS3 9/9, CS4 8/8, CS5 6/6,
    CS6 6/6, CS7 6/6, CS8 4/4, CS9 3/3. Q9BSE5 (human AGMAT): RecName Guanidino acid hydrolase, mitochondrial; AltName
    Arginase, mitochondrial, EC 3.5.3.1 {ECO:0000269|PubMed:36543883}; PATHWAY urea cycle; FunFam 3.40.800.10:FF:000002.
    Rule statistics: 6499 unreviewed proteins.'
confidence: 0.8
corrections:
- date: '2026-11-10'
  withdrawn_claim: The rule inappropriately conflates arginase (EC 3.5.3.1) with agmatinase (EC 3.5.3.11).
  correction: The claim rested on the label of FunFam 3.40.800.10:FF:000002. Its mammalian Swiss-Prot members are
    AGMAT, which Swiss-Prot curates with arginase activity and with the same urea-cycle pathway comment the rule
    assigns.
  error_type: REFUTED_BY_CURATED_ANNOTATION
  evidence:
  - 'UniProtKB Q9BSE5 (AGMAT_HUMAN): AltName Arginase, mitochondrial, EC 3.5.3.1 {ECO:0000269|PubMed:36543883};
    CC PATHWAY Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine'
  - UniProtKB Q9BSE5 DR FunFam 3.40.800.10:FF:000002; Agmatinase
  - 'Swiss-Prot matches of CS9 (FunFam 3.40.800.10:FF:000002 AND Mammalia): 3, all with the pathway comment'
- date: '2026-11-10'
  withdrawn_claim: The rule should be deprecated because it provides no GO term annotations.
  correction: The rule assigns a pathway comment, which the earlier review itself judged accurate. Not emitting
    GO terms is not a reason to retire a correct rule.
  error_type: OTHER
  evidence:
  - 'Live rule annotation: commentType PATHWAY'
  - 'All 9 sets: every Swiss-Prot match carries the comment'
- date: '2026-11-10'
  withdrawn_claim: GO:0052689 (carboxylic acid dimethylamide hydrolase activity) is the molecular function term
    for agmatinase.
  correction: GO:0052689 is carboxylic ester hydrolase activity. Agmatinase activity is GO:0008783.
  error_type: WRONG_IDENTIFIER_MEANING
  evidence:
  - 'QuickGO GO:0052689: carboxylic ester hydrolase activity'
  - 'QuickGO GO:0008783: agmatinase activity'
- date: '2026-11-10'
  withdrawn_claim: Nested InterPro terms in condition set 1 (IPR014033 within IPR006035 within IPR023696) create
    redundancy that is a design flaw.
  correction: Nested conjuncts leave the matched set equal to that of the narrowest term and cannot cause a wrong
    annotation. The live set 1 is IPR006035 AND IPR014033 AND Chordata.
  error_type: CONJUNCTION_IGNORED
  evidence:
  - 'Live rule CS1 (2026-11-09): IPR006035 (Ureohydrolase) AND IPR014033 (Arginase) AND Chordata; 16 Swiss-Prot
    matches, 16 with the pathway comment'
- date: '2026-11-10'
  withdrawn_claim: The taxonomic restrictions are inconsistent and poorly justified, and some FunFam sets have no
    taxon restriction.
  correction: Every live set has a taxon condition, and different signatures having different taxon scopes is not
    an inconsistency.
  error_type: TAXON_MISREAD
  evidence:
  - 'Live rule (2026-11-09): 9 condition sets, each with one taxon condition'