ARBA00022670

id: ARBA00022670
description: >-
  Assigns the UniProt keyword Protease (KW-0645) through 1010 alternative condition sets. About half
  are single InterPro entries or PANTHER families; the rest are conjunctions of two or three conditions,
  some with a taxon.
status: IN_PROGRESS
rule_type: ARBA
rule:
  rule_id: ARBA00022670
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR001907
      curie: InterPro:IPR001907
      label: ATP-dependent Clp protease proteolytic subunit
      negated: false
    - condition_type: INTERPRO
      value: IPR023562
      curie: InterPro:IPR023562
      label: Clp protease proteolytic subunit /Translocation-enhancing protein TepA
      negated: false
    - condition_type: INTERPRO
      value: IPR033135
      curie: InterPro:IPR033135
      label: ClpP, histidine active site
      negated: false
    notes: >-
      UniProtKB release 2026_04: 703 reviewed entries match this set; 703 of them carry keyword KW-0645.
      30331 unreviewed entries match.
  - number: 2
    conditions:
    - condition_type: INTERPRO
      value: IPR018215
      curie: InterPro:IPR018215
      label: ClpP, Ser active site
      negated: false
    - condition_type: INTERPRO
      value: IPR029045
      curie: InterPro:IPR029045
      label: ClpP/crotonase-like domain superfamily
      negated: false
    notes: >-
      UniProtKB release 2026_04: 625 reviewed entries match this set; 625 of them carry keyword KW-0645.
      21284 unreviewed entries match.
  - number: 3
    conditions:
    - condition_type: PANTHER
      value: PTHR10381:SF70
      curie: PANTHER:PTHR10381:SF70
      label: ATP-DEPENDENT CLP PROTEASE PROTEOLYTIC SUBUNIT
      negated: false
    notes: >-
      UniProtKB release 2026_04: 589 reviewed entries match this set; 589 of them carry keyword KW-0645.
      26153 unreviewed entries match.
  - number: 4
    conditions:
    - condition_type: INTERPRO
      value: IPR001353
      curie: InterPro:IPR001353
      label: Proteasome, subunit alpha/beta
      negated: false
    - condition_type: INTERPRO
      value: IPR023333
      curie: InterPro:IPR023333
      label: Proteasome B-type subunit
      negated: false
    - condition_type: PANTHER
      value: PTHR32194:SF0
      curie: PANTHER:PTHR32194:SF0
      label: ATP-DEPENDENT PROTEASE SUBUNIT HSLV
      negated: false
    notes: >-
      UniProtKB release 2026_04: 554 reviewed entries match this set; 554 of them carry keyword KW-0645.
      15211 unreviewed entries match.
  - number: 5
    conditions:
    - condition_type: INTERPRO
      value: IPR000819
      curie: InterPro:IPR000819
      label: Peptidase M17, leucyl aminopeptidase, C-terminal
      negated: false
    - condition_type: INTERPRO
      value: IPR011356
      curie: InterPro:IPR011356
      label: Peptidase M17, leucine aminopeptidase/peptidase B
      negated: false
    - condition_type: INTERPRO
      value: IPR064115
      curie: InterPro:IPR064115
      label: Cytosol aminopeptidase-like, conserved site
      negated: false
    notes: >-
      UniProtKB release 2026_04: 507 reviewed entries match this set; 507 of them carry keyword KW-0645.
      25650 unreviewed entries match.
  - number: 6
    conditions:
    - condition_type: INTERPRO
      value: IPR001915
      curie: InterPro:IPR001915
      label: Peptidase M48
      negated: false
    notes: >-
      UniProtKB release 2026_04: 452 reviewed entries match this set; 452 of them carry keyword KW-0645.
      66417 unreviewed entries match.
  - number: 7
    conditions:
    - condition_type: INTERPRO
      value: IPR023042
      curie: InterPro:IPR023042
      label: Peptidase M17, leucine aminopeptidase
      negated: false
    notes: >-
      UniProtKB release 2026_04: 435 reviewed entries match this set; 435 of them carry keyword KW-0645.
      16239 unreviewed entries match.
  - number: 8
    conditions:
    - condition_type: INTERPRO
      value: IPR022281
      curie: InterPro:IPR022281
      label: ATP-dependent protease subunit HslV
      negated: false
    - condition_type: INTERPRO
      value: IPR029055
      curie: InterPro:IPR029055
      label: Nucleophile aminohydrolases, N-terminal
      negated: false
    notes: >-
      UniProtKB release 2026_04: 434 reviewed entries match this set; 434 of them carry keyword KW-0645.
      9810 unreviewed entries match.
  - number: 9
    conditions:
    - condition_type: PANTHER
      value: PTHR11963:SF23
      curie: PANTHER:PTHR11963:SF23
      label: CYTOSOL AMINOPEPTIDASE
      negated: false
    notes: >-
      UniProtKB release 2026_04: 430 reviewed entries match this set; 430 of them carry keyword KW-0645.
      19552 unreviewed entries match.
  - number: 10
    conditions:
    - condition_type: INTERPRO
      value: IPR001872
      curie: InterPro:IPR001872
      label: Peptidase A8, signal peptidase II
      negated: false
    - condition_type: PANTHER
      value: PTHR33695:SF1
      curie: PANTHER:PTHR33695:SF1
      label: LIPOPROTEIN SIGNAL PEPTIDASE
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: false
    notes: >-
      UniProtKB release 2026_04: 421 reviewed entries match this set; 421 of them carry keyword KW-0645.
      20694 unreviewed entries match.
  go_annotations: []
  entries: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 2151180
  created_date: '2020-05-12'
  modified_date: '2026-07-18'
  retrieved_date: '2026-11-09'
  source_condition_set_count: 1010
review_summary: >-
  The first 10 of the 1010 live condition sets were examined. They select ClpP, HslV, leucyl aminopeptidase,
  peptidase M48 and signal peptidase II families, and every reviewed match carries the Protease keyword
  (5150 of 5150, summed over sets). The other 1000 sets were not examined.
action: UNDECIDED
action_rationale: >-
  The rule was sampled, not examined set by set, so no verdict is given. The sampled sets are sound,
  which removes the grounds of the earlier verdict but does not establish that every set is right.
  The counts are from Swiss-Prot, which is also what ARBA learns its rules from, so they show the
  condition sets are coherent rather than giving an independent error rate for unreviewed entries.
annotation_assessments:
- annotation_kind: KEYWORD
  value: KW-0645
  label: Protease
  assessment: UNDECIDED
  correct_examples:
  - Q16740
  - P0A6G7
  - P38624
  notes: >-
    UniProtKB release 2026_04, reviewed entries matching a set and carrying KW-0645: set 1, Q16740
    (human CLPP) and P0A6G7 (Escherichia coli clpP); set 4, P38624 (Saccharomyces cerevisiae PRE3).
    Per-set counts are in the condition set notes.
corrections:
- date: '2026-11-10'
  withdrawn_claim: >-
    The rule is a single condition set of 502 InterPro domains joined by OR, so any protein with any
    protease-related domain is annotated.
  correction: >-
    The rule is a list of alternative condition sets, and the conditions inside a set are joined by
    AND. The live rule has 1010 sets; 497 require two or three conditions together.
  error_type: CONJUNCTION_IGNORED
  evidence:
  - >-
    UniProt ARBA API, ARBA00022670, modified 2026-07-18, retrieved 2026-11-09: 1010 condition sets
    (513 with one condition, 309 with two, 188 with three); every condition has a single value.
- date: '2026-11-10'
  withdrawn_claim: The rule has no taxonomic restrictions.
  correction: 236 of the 1010 live condition sets include a taxon condition.
  error_type: TAXON_MISREAD
  evidence:
  - >-
    UniProt ARBA API, ARBA00022670: 236 condition sets contain a condition of type taxon, for example
    set 10 (taxon Bacteria).
- date: '2026-11-10'
  withdrawn_claim: >-
    Treating pepsin, trypsin and other mechanistically distinct proteases the same is a design flaw,
    and the classification literature contradicts the rule.
  correction: >-
    All of these enzymes are proteases, which is all the keyword says. That proteases fall into mechanistic
    classes does not make the keyword wrong for any of them. The source given for the contradiction
    was an unattributed sentence labelled as a database, not a retrievable publication.
  error_type: GENERAL_IS_NOT_WRONG
  evidence:
  - >-
    UniProtKB release 2026_04: in the ten sets examined every reviewed match carries keyword KW-0645;
    per-set counts are in the condition set notes.
- date: '2026-11-10'
  withdrawn_claim: >-
    Inactive zymogens and other non-catalytic proteins with protease domains would be annotated, giving
    massive false positives across 2.47 million proteins.
  correction: >-
    No falsely annotated protein was named and no rate was measured. Zymogens are protease precursors
    and carry the Protease keyword in Swiss-Prot.
  error_type: UNEXAMINED_RULE
  evidence:
  - The old file recorded no condition sets and no matched entries.
- date: '2026-11-10'
  withdrawn_claim: The rule is deficient because it assigns a keyword and not GO terms.
  correction: The consequent is a UniProt keyword by design.
  error_type: OTHER
  evidence:
  - 'UniProt ARBA API, ARBA00022670: single annotation, keyword KW-0645 Protease.'