ARBA00047230 phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity (GO:0052629)

id: ARBA00047230
description: 'Assigns GO:0052629 phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity to primate
  and eukaryotic myotubularin-family proteins through four alternative condition sets: the myotubularin-like
  phosphatase domain together with the protein-tyrosine phosphatase active site (Primates), and three
  myotubularin FunFams (Primates, Haplorrhini, Eukaryota).'
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00047230
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR010569
      curie: InterPro:IPR010569
      label: Myotubularin-like, phosphatase domain
      interpro_type: DOMAIN
      negated: false
    - condition_type: INTERPRO
      value: IPR016130
      curie: InterPro:IPR016130
      label: Protein-tyrosine phosphatase, active site
      interpro_type: ACTIVE_SITE
      negated: false
    - condition_type: TAXON
      value: '9443'
      curie: NCBITaxon:9443
      label: Primates
      negated: false
    notes: 'UniProtKB query, November 2026: 11 Swiss-Prot and 649 TrEMBL entries match. QuickGO, GO:0052629
      or a descendant on the Swiss-Prot entries: 7 with experimental evidence, 3 with other manual evidence
      only, 1 with IEA only, 0 with none. Examples: Q13614 (MTMR2_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, EXP, PMID:21372139; Q13615 (MTMR3_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, IDA, PMID:11676921; Q9NYA4 (MTMR4_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, IDA, PMID:20736309.'
  - number: 2
    conditions:
    - condition_type: FUNFAM
      value: 2.30.29.30:FF:000038
      curie: CATH.FUNFAM:2.30.29.30:FF:000038
      label: Myotubularin 1, isoform CRA_a
      negated: false
    - condition_type: TAXON
      value: '9443'
      curie: NCBITaxon:9443
      label: Primates
      negated: false
    notes: 'UniProtKB query, November 2026: 5 Swiss-Prot and 279 TrEMBL entries match. QuickGO, GO:0052629
      or a descendant on the Swiss-Prot entries: 3 with experimental evidence, 2 with other manual evidence
      only, 0 with IEA only, 0 with none. Examples: Q13614 (MTMR2_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, EXP, PMID:21372139; Q13613 (MTMR1_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, IDA, PMID:27018598; Q13496 (MTM1_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, EXP, PMID:14722070.'
  - number: 3
    conditions:
    - condition_type: FUNFAM
      value: 2.30.29.30:FF:000135
      curie: CATH.FUNFAM:2.30.29.30:FF:000135
      label: Myotubularin related protein 6
      negated: false
    - condition_type: TAXON
      value: '376913'
      curie: NCBITaxon:376913
      label: Haplorrhini
      negated: false
    notes: 'UniProtKB query, November 2026: 4 Swiss-Prot and 153 TrEMBL entries match. QuickGO, GO:0052629
      or a descendant on the Swiss-Prot entries: 2 with experimental evidence, 1 with other manual evidence
      only, 1 with IEA only, 0 with none. Examples: Q9Y217 (MTMR6_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, EXP, PMID:22647598; Q96EF0 (MTMR8_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, EXP, PMID:22647598.'
  - number: 4
    conditions:
    - condition_type: FUNFAM
      value: 3.30.40.10:FF:000073
      curie: CATH.FUNFAM:3.30.40.10:FF:000073
      label: myotubularin-related protein 4 isoform X2
      negated: false
    - condition_type: TAXON
      value: '2759'
      curie: NCBITaxon:2759
      label: Eukaryota
      negated: false
    notes: 'UniProtKB query, November 2026: 19 Swiss-Prot and 3173 TrEMBL entries match. QuickGO, GO:0052629
      or a descendant on the Swiss-Prot entries: 2 with experimental evidence, 4 with other manual evidence
      only, 13 with IEA only, 0 with none. Examples: Q13615 (MTMR3_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, IDA, PMID:11676921; Q9NYA4 (MTMR4_HUMAN) GO:0052629 phosphatidylinositol-3,5-bisphosphate
      3-phosphatase activity, IDA, PMID:20736309.'
  go_annotations:
  - go_id: GO:0052629
    go_label: phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity
    aspect: MF
  entries: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 0
  created_date: '2024-08-14'
  modified_date: '2026-07-18'
  retrieved_date: '2026-11-09'
  source_condition_set_count: 4
review_summary: 'All four live condition sets were examined. Every Swiss-Prot entry matching any set carries
  GO:0052629, and each set contains members annotated from experiments (for example MTMR2, MTMR3, MTMR4,
  MTMR6, MTMR8, MTM1, MTMR1). In set 1 the active-site condition is what separates the active myotubularins
  from the catalytically inactive family members: of 63 Swiss-Prot entries with IPR010569, 37 also have
  IPR016130, and the six human entries without it are the proteins UniProt names "Inactive phosphatidylinositol
  3-phosphatase" (MTMR5, 9, 10, 11, 12, 13).'
action: ACCEPT
action_rationale: Each condition set selects myotubularins with curated, mostly experimental, annotation
  to the rule's term, and no Swiss-Prot match lacks the term. The second condition of set 1 should stay,
  because dropping it would extend a catalytic activity to the inactive paralogs.
literature_support:
  assessment: STRONG
  notes: 'Curated GO annotations on matched Swiss-Prot entries: Q13614 (MTMR2) GO:0052629 EXP PMID:21372139;
    Q13615 (MTMR3) GO:0052629 IDA PMID:11676921; Q9NYA4 (MTMR4) GO:0052629 IDA PMID:20736309; Q13496 (MTM1)
    GO:0052629 EXP PMID:14722070; Q9Y217 (MTMR6) GO:0052629 EXP PMID:22647598 (QuickGO, November 2026).'
go_specificity:
  assessment: APPROPRIATE
  notes: The experimental annotations on the matched proteins are to GO:0052629 itself.
annotation_assessments:
- annotation_kind: GO_TERM
  value: GO:0052629
  label: phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity
  assessment: CORRECT
  correct_examples:
  - Q13614
  - Q13615
  - Q9NYA4
  - Q9Y217
  - Q13496
  - Q96EF0
  - Q13613
  notes: Per-set receipts are in rule.condition_sets[].notes. Accessions listed are Swiss-Prot matches
    with experimental evidence for GO:0052629 in QuickGO.
confidence: 0.85
corrections:
- date: '2026-11-10'
  withdrawn_claim: The dual domain requirement in condition set 1 is overly restrictive and may exclude
    legitimate myotubularin proteins; remove the PTP domain condition.
  correction: The second condition excludes the catalytically inactive myotubularins, which must not receive
    a phosphatase activity term. Removing it would create false positives.
  error_type: CONJUNCTION_IGNORED
  evidence:
  - 'UniProtKB query (xref:interpro-IPR010569) AND (reviewed:true): 63 entries'
  - 'UniProtKB query (xref:interpro-IPR010569) AND (xref:interpro-IPR016130) AND (reviewed:true): 37 entries'
  - 'Human Swiss-Prot entries with IPR010569 but not IPR016130: O95248 (MTMR5), Q86WG5 (MTMR13), Q96QG7
    (MTMR9), Q9C0I1 (MTMR12), A4FU01 (MTMR11), Q9NXD2 (MTMR10); UniProt names each "Inactive phosphatidylinositol
    3-phosphatase"'
  - 'Live rule set 1: IPR010569 AND IPR016130 AND Primates (rest.uniprot.org/arba/ARBA00047230, 2026-11-09)'
- date: '2026-11-10'
  withdrawn_claim: The two CATH FunFams are completely disjoint, so the rule conflates distinct annotation
    patterns and should be split; condition overlap is significant.
  correction: Condition sets are alternatives, so sets that match different proteins are expected and
    are not overlap. Each set on its own selects annotated myotubularins.
  error_type: OTHER
  evidence:
  - Per-set Swiss-Prot counts and evidence in rule.condition_sets[].notes
- date: '2026-11-10'
  withdrawn_claim: Both FunFams show 100% containment in the GO term, suggesting redundancy with simpler
    domain-based annotations.
  correction: Full containment in the GO term means every matched Swiss-Prot protein has the function;
    it is evidence for the rule. No InterPro2GO mapping gives GO:0052629 for these entries.
  error_type: OTHER
  evidence:
  - 'rules/arba/_interpro2go.txt: IPR000387 and IPR016130 map only to GO:0016311 dephosphorylation; IPR010569
    has no mapping'
- date: '2026-11-10'
  withdrawn_claim: The Primates restrictions lack justification and all sets should be widened to Eukaryota.
  correction: No evidence was given that every eukaryotic match is active on PtdIns(3,5)P2. The restriction
    limits where the rule fires; it is not an error in what it asserts.
  error_type: TAXON_MISREAD
  evidence:
  - 'Live rule sets: Primates, Primates, Haplorrhini, Eukaryota'
- date: '2026-11-10'
  withdrawn_claim: Condition set 1 uses IPR000387 and the rule has three condition sets.
  correction: The live rule has four sets and set 1 uses IPR016130 (Protein-tyrosine phosphatase, active
    site).
  error_type: STALE_RULE_VERSION
  evidence:
  - rest.uniprot.org/arba/ARBA00047230 retrieved 2026-11-09, modifiedDate 2026-07-18