ARBA00000900

id: ARBA00000900
description: >-
  Assigns the catalytic activity EC 2.3.2.27 (RING-type E3 ubiquitin transferase) through 304 alternative
  condition sets built from InterPro entries, PANTHER families and CATH FunFams, 55 of them with a
  taxon.
status: IN_PROGRESS
rule_type: ARBA
rule:
  rule_id: ARBA00000900
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR001841
      curie: InterPro:IPR001841
      label: Zinc finger, RING-type
      negated: false
    - condition_type: INTERPRO
      value: IPR003877
      curie: InterPro:IPR003877
      label: SPRY domain
      negated: false
    - condition_type: INTERPRO
      value: IPR027370
      curie: InterPro:IPR027370
      label: Zinc finger, RING-type, eukaryotic
      negated: false
    notes: >-
      UniProtKB release 2026_04: 67 reviewed entries match this set; 67 of them carry EC 2.3.2.27.
      16909 unreviewed entries match.
  - number: 2
    conditions:
    - condition_type: INTERPRO
      value: IPR003613
      curie: InterPro:IPR003613
      label: U-box domain
      negated: false
    - condition_type: INTERPRO
      value: IPR013083
      curie: InterPro:IPR013083
      label: Zinc finger, RING/FYVE/PHD-type
      negated: false
    - condition_type: INTERPRO
      value: IPR016024
      curie: InterPro:IPR016024
      label: Armadillo-type fold
      negated: false
    notes: >-
      UniProtKB release 2026_04: 53 reviewed entries match this set; 53 of them carry EC 2.3.2.27.
      23035 unreviewed entries match.
  - number: 3
    conditions:
    - condition_type: INTERPRO
      value: IPR013956
      curie: InterPro:IPR013956
      label: E3 ubiquitin ligase Bre1
      negated: false
    notes: >-
      UniProtKB release 2026_04: 36 reviewed entries match this set; 36 of them carry EC 2.3.2.27.
      6972 unreviewed entries match.
  - number: 4
    conditions:
    - condition_type: INTERPRO
      value: IPR013010
      curie: InterPro:IPR013010
      label: Zinc finger, SIAH-type
      negated: false
    - condition_type: INTERPRO
      value: IPR049548
      curie: InterPro:IPR049548
      label: E3 ubiquitin-protein ligase Sina-like, RING finger
      negated: false
    notes: >-
      UniProtKB release 2026_04: 35 reviewed entries match this set; 35 of them carry EC 2.3.2.27.
      7845 unreviewed entries match.
  - number: 5
    conditions:
    - condition_type: INTERPRO
      value: IPR044600
      curie: InterPro:IPR044600
      label: RING-H2 finger protein ATL1/ATL16-like
      negated: false
    - condition_type: TAXON
      value: Streptophyta
      curie: NCBITaxon:35493
      label: Streptophyta
      negated: false
    notes: >-
      UniProtKB release 2026_04: 24 reviewed entries match this set; 24 of them carry EC 2.3.2.27.
      9550 unreviewed entries match.
  - number: 6
    conditions:
    - condition_type: INTERPRO
      value: IPR011042
      curie: InterPro:IPR011042
      label: Six-bladed beta-propeller, TolB-like
      negated: false
    - condition_type: INTERPRO
      value: IPR017907
      curie: InterPro:IPR017907
      label: Zinc finger, RING-type, conserved site
      negated: false
    - condition_type: TAXON
      value: Chordata
      curie: NCBITaxon:7711
      label: Chordata
      negated: false
    notes: >-
      UniProtKB release 2026_04: 23 reviewed entries match this set; 23 of them carry EC 2.3.2.27.
      4510 unreviewed entries match.
  - number: 12
    conditions:
    - condition_type: INTERPRO
      value: IPR029487
      curie: InterPro:IPR029487
      label: Novel E3 ligase domain
      negated: false
    - condition_type: INTERPRO
      value: IPR032675
      curie: InterPro:IPR032675
      label: Leucine-rich repeat domain superfamily
      negated: false
    - condition_type: TAXON
      value: Gammaproteobacteria
      curie: NCBITaxon:1236
      label: Gammaproteobacteria
      negated: false
    notes: >-
      UniProtKB release 2026_04: 16 reviewed entries match this set; 16 of them carry EC 2.3.2.27.
      1081 unreviewed entries match. Bacterial effector E3 ligases of the IpaH/SspH type.
  go_annotations: []
  catalytic_activity_annotations:
  - reaction_name: >-
      S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2
      ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.
    ec_number: 2.3.2.27
  entries: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 356485
  created_date: '2020-05-12'
  modified_date: '2026-07-18'
  retrieved_date: '2026-11-09'
  source_condition_set_count: 304
review_summary: >-
  7 of the 304 live condition sets were examined: the first six and the one bacterial set. They select
  RING-finger, U-box, Bre1, SIAH and plant ATL families and the bacterial novel E3 ligase effectors,
  and every reviewed match carries EC 2.3.2.27 (254 of 254, summed over sets). The rule contains no
  HECT-domain condition. The other 297 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: CATALYTIC_ACTIVITY
  value: 2.3.2.27
  label: RING-type E3 ubiquitin transferase
  assessment: UNDECIDED
  correct_examples:
  - Q9C030
  - O15344
  - O22193
  - D0ZPH9
  - P18014
  notes: >-
    UniProtKB release 2026_04, reviewed entries matching a set and carrying EC 2.3.2.27: set 1, Q9C030
    (human TRIM6) and O15344 (human MID1); set 2, O22193 (Arabidopsis PUB4); set 12, D0ZPH9 (Salmonella
    sspH2) and P18014 (Shigella ipaH7.8). Per-set counts are in the condition set notes.
corrections:
- date: '2026-11-10'
  withdrawn_claim: >-
    The rule unifies RING, HECT and U-box ligases, which have fundamentally different catalytic mechanisms,
    and so is mechanistically incoherent.
  correction: >-
    The live rule has no HECT condition. RING and U-box ligases share the reaction of EC 2.3.2.27,
    direct transfer from the E2 to the substrate; HECT ligases have their own number, EC 2.3.2.26.
  error_type: UNEXAMINED_RULE
  evidence:
  - >-
    UniProt ARBA API, ARBA00000900, retrieved 2026-11-09: no condition on IPR000569 (HECT domain)
    or on a CATH FunFam of superfamily 3.30.2410.10; conditions on IPR001841 (Zinc finger, RING-type)
    and IPR003613 (U-box domain) are present.
  - >-
    Rule annotation: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine
    = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine,
    EC 2.3.2.27.
  - 'UniProtKB release 2026_04: 131 reviewed entries carry EC 2.3.2.26.'
- date: '2026-11-10'
  withdrawn_claim: >-
    The rule should be deprecated although its biological basis is sound and all targets share the
    activity.
  correction: >-
    If all targets share the activity the annotation is correct, and that is a reason to keep the
    rule. No wrongly annotated protein was named.
  error_type: GENERAL_IS_NOT_WRONG
  evidence:
  - >-
    UniProtKB release 2026_04: in the seven sets examined every reviewed match carries EC 2.3.2.27.
- date: '2026-11-10'
  withdrawn_claim: 298 condition sets create a high false positive risk and make the rule unmaintainable.
  correction: The number of sets is not evidence about accuracy.
  error_type: SIZE_AS_EVIDENCE
  evidence:
  - >-
    UniProt ARBA API, ARBA00000900: 304 condition sets, 173 of them conjunctions of two or three conditions.
- date: '2026-11-10'
  withdrawn_claim: >-
    Applying the rule to bacteria is inappropriate because bacterial proteins lack a ubiquitin system.
  correction: >-
    The one bacterial set selects secreted effector ligases of Gammaproteobacteria that ubiquitinate
    host proteins, and their reviewed members carry EC 2.3.2.27.
  error_type: TAXON_MISREAD
  evidence:
  - >-
    Set 12: IPR029487 (Novel E3 ligase domain) AND IPR032675 (Leucine-rich repeat domain superfamily)
    AND taxon Gammaproteobacteria; 16 of 16 reviewed matches carry EC 2.3.2.27, for example D0ZPH9
    and P18014.
- date: '2026-11-10'
  withdrawn_claim: The rule lacks GO:0004842, the GO term equivalent to its EC number.
  correction: >-
    EC 2.3.2.27 is cross-referenced from GO:0061630 (ubiquitin protein ligase activity), a more specific
    term than GO:0004842 (ubiquitin-protein transferase activity). The rule has no GO annotation of
    its own; GO terms follow from the EC number.
  error_type: ONTOLOGY_MISREAD
  evidence:
  - >-
    QuickGO: GO:0061630 has EC cross-references 2.3.2.26, 2.3.2.27, 2.3.2.31, 2.3.2.33 and 2.3.2.36;
    GO:0004842 has none.