ARBA00026372 protein carboxyl O-methyltransferase activity (GO:0051998)

id: ARBA00026372
description: >-
  Assigns GO:0051998 (protein carboxyl O-methyltransferase activity) through six alternative condition
  sets covering three enzyme families: isoprenylcysteine carboxyl methyltransferases (sets 1, 3, 4),
  protein-L-isoaspartate O-methyltransferases (sets 2, 5) and leucine carboxyl methyltransferase 1
  (set 6).
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00026372
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR007269
      curie: InterPro:IPR007269
      label: Isoprenylcysteine carboxyl methyltransferase
      negated: false
    - condition_type: INTERPRO
      value: IPR025770
      curie: InterPro:IPR025770
      label: Protein-S-isoprenylcysteine O-methyltransferase
      negated: false
    - condition_type: PANTHER
      value: PTHR12714
      curie: PANTHER:PTHR12714
      label: PROTEIN-S ISOPRENYLCYSTEINE O-METHYLTRANSFERASE
      negated: false
    notes: >-
      UniProtKB release 2026_04: 12 reviewed entries match this set; 12 of them carry GO:0051998 or
      a descendant, 11 of those by a manual-evidence GO annotation. 3634 unreviewed entries match.
    pairwise_overlap:
    - condition_a: IPR007269
      condition_b: IPR025770
      protein_database: SWISSPROT
      count_a: 16
      count_b: 12
      intersection_count: 12
      a_minus_b_count: 4
      b_minus_a_count: 0
      jaccard_similarity: 0.75
      containment_a_in_b: 0.75
      containment_b_in_a: 1.0
      interpretation: SUBSET
    - condition_a: IPR007269
      condition_b: PTHR12714
      protein_database: SWISSPROT
      count_a: 16
      count_b: 19
      intersection_count: 14
      a_minus_b_count: 2
      b_minus_a_count: 5
      jaccard_similarity: 0.6666666666666666
      containment_a_in_b: 0.875
      containment_b_in_a: 0.7368421052631579
      interpretation: HIGH_OVERLAP
    - condition_a: IPR025770
      condition_b: PTHR12714
      protein_database: SWISSPROT
      count_a: 12
      count_b: 19
      intersection_count: 12
      a_minus_b_count: 0
      b_minus_a_count: 7
      jaccard_similarity: 0.631578947368421
      containment_a_in_b: 1.0
      containment_b_in_a: 0.631578947368421
      interpretation: SUBSET
  - number: 2
    conditions:
    - condition_type: FUNFAM
      value: 3.40.50.150:FF:000027
      curie: CATH.FunFam:3.40.50.150:FF:000027
      label: Protein-L-isoaspartate O-methyltransferase
      negated: false
    - condition_type: TAXON
      value: Eukaryota
      curie: NCBITaxon:2759
      label: Eukaryota
      negated: false
    notes: >-
      UniProtKB release 2026_04: 12 reviewed entries match this set; 12 of them carry GO:0051998 or
      a descendant, 12 of those by a manual-evidence GO annotation. 3216 unreviewed entries match.
  - number: 3
    conditions:
    - condition_type: FUNFAM
      value: 1.20.120.1630:FF:000007
      curie: CATH.FunFam:1.20.120.1630:FF:000007
      label: Protein-S-isoprenylcysteine O-methyltransferase
      negated: false
    notes: >-
      UniProtKB release 2026_04: 6 reviewed entries match this set; 6 of them carry GO:0051998 or
      a descendant, 6 of those by a manual-evidence GO annotation. 759 unreviewed entries match.
  - number: 4
    conditions:
    - condition_type: FUNFAM
      value: 1.20.120.1630:FF:000018
      curie: CATH.FunFam:1.20.120.1630:FF:000018
      label: Protein-S-isoprenylcysteine O-methyltransferase
      negated: false
    - condition_type: TAXON
      value: Fungi
      curie: NCBITaxon:4751
      label: Fungi
      negated: false
    notes: >-
      UniProtKB release 2026_04: 2 reviewed entries match this set; 2 of them carry GO:0051998 or
      a descendant, 2 of those by a manual-evidence GO annotation. 48 unreviewed entries match.
  - number: 5
    conditions:
    - condition_type: FUNFAM
      value: 3.40.50.150:FF:000235
      curie: CATH.FunFam:3.40.50.150:FF:000235
      label: Protein-L-isoaspartate O-methyltransferase
      negated: false
    - condition_type: TAXON
      value: Metazoa
      curie: NCBITaxon:33208
      label: Metazoa
      negated: false
    notes: >-
      UniProtKB release 2026_04: 2 reviewed entries match this set; 2 of them carry GO:0051998 or
      a descendant, 2 of those by a manual-evidence GO annotation. 86 unreviewed entries match.
  - number: 6
    conditions:
    - condition_type: FUNFAM
      value: 3.40.50.150:FF:000092
      curie: CATH.FunFam:3.40.50.150:FF:000092
      label: Leucine carboxyl methyltransferase 1
      negated: false
    notes: >-
      UniProtKB release 2026_04: 6 reviewed entries match this set; 6 of them carry GO:0051998 or
      a descendant, 6 of those by a manual-evidence GO annotation. 1987 unreviewed entries match.
  go_annotations:
  - go_id: GO:0051998
    go_label: protein carboxyl O-methyltransferase activity
    aspect: MF
  entries:
  - id: 1.20.120.1630:FF:000007
    type: FUNFAM
    label: Protein-S-isoprenylcysteine O-methyltransferase
    appears_in_condition_sets:
    - 3
    protein_count: 6
    related_entries:
    - relationship: PREDICTS
      target_id: IPR007269
      containment: 0.375
      jaccard_similarity: 0.375
      intersection_count: 6
      exclusive_count: 10
    - relationship: PREDICTS
      target_id: IPR025770
      containment: 0.5
      jaccard_similarity: 0.5
      intersection_count: 6
      exclusive_count: 6
    - relationship: PREDICTS
      target_id: PTHR12714
      containment: 0.316
      jaccard_similarity: 0.316
      intersection_count: 6
      exclusive_count: 13
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000027
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 6
    - relationship: EQUIV
      target_id: 1.20.120.1630:FF:000018
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 6
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000235
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 6
    - relationship: PREDICTS
      target_id: GO:0051998
      containment: 1.0
      jaccard_similarity: 0.015
      intersection_count: 6
      exclusive_count: 0
  - id: 1.20.120.1630:FF:000018
    type: FUNFAM
    label: Protein-S-isoprenylcysteine O-methyltransferase
    appears_in_condition_sets:
    - 4
    protein_count: 2
    related_entries:
    - relationship: PREDICTS
      target_id: IPR007269
      containment: 0.125
      jaccard_similarity: 0.125
      intersection_count: 2
      exclusive_count: 14
    - relationship: PREDICTS
      target_id: IPR025770
      containment: 0.167
      jaccard_similarity: 0.167
      intersection_count: 2
      exclusive_count: 10
    - relationship: PREDICTS
      target_id: PTHR12714
      containment: 0.105
      jaccard_similarity: 0.105
      intersection_count: 2
      exclusive_count: 17
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000027
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: EQUIV
      target_id: 1.20.120.1630:FF:000007
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000235
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: PREDICTS
      target_id: GO:0051998
      containment: 1.0
      jaccard_similarity: 0.005
      intersection_count: 2
      exclusive_count: 0
  - id: 3.40.50.150:FF:000027
    type: FUNFAM
    label: Protein-L-isoaspartate O-methyltransferase
    appears_in_condition_sets:
    - 2
    protein_count: 12
    related_entries:
    - relationship: EQUIV
      target_id: IPR007269
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 12
    - relationship: EQUIV
      target_id: IPR025770
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 12
    - relationship: EQUIV
      target_id: PTHR12714
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 12
    - relationship: EQUIV
      target_id: 1.20.120.1630:FF:000007
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 12
    - relationship: EQUIV
      target_id: 1.20.120.1630:FF:000018
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 12
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000235
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 12
    - relationship: PREDICTS
      target_id: GO:0051998
      containment: 1.0
      jaccard_similarity: 0.029
      intersection_count: 12
      exclusive_count: 0
  - id: 3.40.50.150:FF:000235
    type: FUNFAM
    label: Protein-L-isoaspartate O-methyltransferase
    appears_in_condition_sets:
    - 5
    protein_count: 2
    related_entries:
    - relationship: EQUIV
      target_id: IPR007269
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: EQUIV
      target_id: IPR025770
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: EQUIV
      target_id: PTHR12714
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000027
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: EQUIV
      target_id: 1.20.120.1630:FF:000007
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: EQUIV
      target_id: 1.20.120.1630:FF:000018
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: PREDICTS
      target_id: GO:0051998
      containment: 1.0
      jaccard_similarity: 0.005
      intersection_count: 2
      exclusive_count: 0
  - id: IPR007269
    type: INTERPRO
    label: Isoprenylcysteine carboxyl methyltransferase
    appears_in_condition_sets:
    - 1
    protein_count: 16
    related_entries:
    - relationship: PREDICTED_BY
      target_id: IPR025770
      containment: 1.0
      jaccard_similarity: 0.75
      intersection_count: 12
      exclusive_count: 0
    - relationship: PREDICTS
      target_id: PTHR12714
      containment: 0.875
      jaccard_similarity: 0.667
      intersection_count: 14
      exclusive_count: 2
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000027
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 16
    - relationship: PREDICTED_BY
      target_id: 1.20.120.1630:FF:000007
      containment: 1.0
      jaccard_similarity: 0.375
      intersection_count: 6
      exclusive_count: 0
    - relationship: PREDICTED_BY
      target_id: 1.20.120.1630:FF:000018
      containment: 1.0
      jaccard_similarity: 0.125
      intersection_count: 2
      exclusive_count: 0
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000235
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 16
    - relationship: PREDICTS
      target_id: GO:0051998
      containment: 1.0
      jaccard_similarity: 0.039
      intersection_count: 16
      exclusive_count: 0
  - id: IPR025770
    type: INTERPRO
    label: Protein-S-isoprenylcysteine O-methyltransferase
    appears_in_condition_sets:
    - 1
    protein_count: 12
    related_entries:
    - relationship: PREDICTS
      target_id: IPR007269
      containment: 0.75
      jaccard_similarity: 0.75
      intersection_count: 12
      exclusive_count: 4
    - relationship: PREDICTS
      target_id: PTHR12714
      containment: 1.0
      jaccard_similarity: 0.632
      intersection_count: 12
      exclusive_count: 0
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000027
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 12
    - relationship: PREDICTED_BY
      target_id: 1.20.120.1630:FF:000007
      containment: 1.0
      jaccard_similarity: 0.5
      intersection_count: 6
      exclusive_count: 0
    - relationship: PREDICTED_BY
      target_id: 1.20.120.1630:FF:000018
      containment: 1.0
      jaccard_similarity: 0.167
      intersection_count: 2
      exclusive_count: 0
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000235
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 12
    - relationship: PREDICTS
      target_id: GO:0051998
      containment: 1.0
      jaccard_similarity: 0.029
      intersection_count: 12
      exclusive_count: 0
  - id: PTHR12714
    type: PANTHER
    appears_in_condition_sets:
    - 1
    protein_count: 19
    related_entries:
    - relationship: PREDICTED_BY
      target_id: IPR007269
      containment: 0.737
      jaccard_similarity: 0.667
      intersection_count: 14
      exclusive_count: 5
    - relationship: PREDICTED_BY
      target_id: IPR025770
      containment: 0.632
      jaccard_similarity: 0.632
      intersection_count: 12
      exclusive_count: 7
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000027
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: PREDICTED_BY
      target_id: 1.20.120.1630:FF:000007
      containment: 1.0
      jaccard_similarity: 0.316
      intersection_count: 6
      exclusive_count: 0
    - relationship: PREDICTED_BY
      target_id: 1.20.120.1630:FF:000018
      containment: 1.0
      jaccard_similarity: 0.105
      intersection_count: 2
      exclusive_count: 0
    - relationship: EQUIV
      target_id: 3.40.50.150:FF:000235
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: PREDICTS
      target_id: GO:0051998
      containment: 0.737
      jaccard_similarity: 0.034
      intersection_count: 14
      exclusive_count: 5
    label: PROTEIN-S ISOPRENYLCYSTEINE O-METHYLTRANSFERASE
  reviewed_protein_count: 0
  unreviewed_protein_count: 0
  created_date: '2021-10-20'
  modified_date: '2026-07-18'
  retrieved_date: '2026-11-09'
  source_condition_set_count: 6
review_summary: >-
  All six live condition sets were examined. They match 40 reviewed entries in total and every one
  carries GO:0051998 or a descendant, 39 by manual evidence. GO:0051998 is the common parent of the
  specific activities of the three families, so the annotation is true for every family the rule covers.
  More specific terms exist for each family and are already supplied by InterPro2GO for two of them.
action: ACCEPT
action_rationale: >-
  The annotation is correct for all three families. It is less specific than the per-family child
  terms, but a general true term is not an error, and one rule spanning three families can only use
  their shared parent. 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.
suggested_modifications:
- >-
  Optional refinement, not a correction: split by family so that sets 1, 3 and 4 give GO:0004671,
  sets 2 and 5 give GO:0004719 and set 6 gives GO:0018423.
go_specificity:
  assessment: APPROPRIATE
  notes: >-
    GO:0004671 (protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity), GO:0004719
    (protein-L-isoaspartate (D-aspartate) O-methyltransferase activity) and GO:0018423 (protein C-terminal
    leucine carboxyl O-methyltransferase activity) each have GO:0051998 as an is_a ancestor (QuickGO).
    The rule term is the most specific term shared by the three families it covers.
annotation_assessments:
- annotation_kind: GO_TERM
  value: GO:0051998
  label: protein carboxyl O-methyltransferase activity
  assessment: CORRECT
  matched_protein_count: 40
  incorrect_protein_count: 0
  notes: >-
    UniProtKB release 2026_04: the six sets match 12, 12, 6, 2, 2 and 6 reviewed entries; all 40 carry
    GO:0051998 or a descendant, 39 by manual-evidence annotation. In rules/arba/_interpro2go.txt,
    IPR007269 and IPR025770 map to GO:0004671 and IPR000682 maps to GO:0004719.
confidence: 0.8
corrections:
- date: '2026-11-10'
  withdrawn_claim: >-
    The rule should be deprecated to prevent false annotations, because it puts two mechanistically
    distinct enzyme families under one term.
  correction: >-
    No false annotation was shown. Both families, and the leucine carboxyl methyltransferase family
    now also in the rule, methylate a carboxyl group on a protein, which is what GO:0051998 says.
    The argument made was that the term is general, and that is not a reason to deprecate.
  error_type: GENERAL_IS_NOT_WRONG
  evidence:
  - >-
    QuickGO: GO:0051998 definition, Catalysis of the transfer of a methyl group to a carboxyl group
    on a protein.
  - >-
    QuickGO ancestors: GO:0004671, GO:0004719 and GO:0018423 are each is_a descendants of GO:0051998.
  - 'UniProtKB release 2026_04: 40 of 40 reviewed matches carry GO:0051998 or a descendant.'
- date: '2026-11-10'
  withdrawn_claim: >-
    The complete disjointness between the ICMT and PIMT condition sets, and between two ICMT FunFams,
    shows the rule is incoherent.
  correction: >-
    Alternative condition sets are expected to select different proteins. Disjointness between them
    is not a defect.
  error_type: OTHER
  evidence:
  - 'UniProt ARBA API: the consequent applies when any one condition set is satisfied.'
- date: '2026-11-10'
  withdrawn_claim: >-
    IPR025770 is a complete subset of IPR007269, so condition set 1 is redundant and badly designed.
  correction: >-
    The two conditions are combined with AND inside one set. A nested pair makes the set equal to
    its narrower member; it does not make any annotation wrong.
  error_type: CONJUNCTION_IGNORED
  evidence:
  - 'UniProt ARBA API, ARBA00026372 set 1: IPR007269 AND IPR025770 AND PANTHER:PTHR12714.'
- date: '2026-11-10'
  withdrawn_claim: The literature contradicts the rule.
  correction: >-
    The papers cited describe the two enzymes as carboxyl methyltransferases acting on proteins, which
    agrees with the term. They show that the families differ, not that the annotation is false.
  error_type: GENERAL_IS_NOT_WRONG
  evidence:
  - >-
    PMID:22195972 and PMID:31234761 were cited by the old review for the mechanism of each family;
    neither was cited for a statement that the enzymes lack protein carboxyl O-methyltransferase activity.
- date: '2026-11-10'
  withdrawn_claim: Condition set 1 has no taxon restriction and would annotate all domains of life.
  correction: >-
    Set 1 requires membership of PANTHER family PTHR12714 together with two InterPro entries for the
    same enzyme, so it is limited by family rather than by taxon.
  error_type: CONJUNCTION_IGNORED
  evidence:
  - >-
    PANTHER:PTHR12714 name: PROTEIN-S ISOPRENYLCYSTEINE O-METHYLTRANSFERASE (interpro/panther/panther.obo).