ARBA00035068 phosphatidylinositol-3-phosphate phosphatase activity (GO:0004438)

id: ARBA00035068
description: 'Assigns GO:0004438 phosphatidylinositol-3-phosphate phosphatase activity through two condition sets:
  CATH FunFam 2.30.29.30:FF:000038 in Primates (MTM1, MTMR1, MTMR2) and CATH FunFam 3.30.40.10:FF:000073 in Eukaryota
  (the FYVE-domain region of MTMR3 and MTMR4).'
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00035068
  condition_sets:
  - number: 1
    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: Primates
      curie: NCBITaxon:9443
      label: Primates
      negated: false
    notes: 'Swiss-Prot entries matching this set (2026-11-09): 5. 5 carry GO:0004438 or a descendant with evidence
      other than ARBA (5 non-IEA, 0 other IEA); 0 carry it only from ARBA; 0 do not carry it. UniProtKB entries
      matching: 284. This FunFam lies in CATH superfamily 2.30.29.30 and all five matches are MTM1, MTMR1 or MTMR2.'
  - number: 2
    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: Eukaryota
      curie: NCBITaxon:2759
      label: Eukaryota
      negated: false
    notes: 'Swiss-Prot entries matching this set (2026-11-09): 19. 6 carry GO:0004438 or a descendant with evidence
      other than ARBA (6 non-IEA, 0 other IEA); 13 carry it only from ARBA; 0 do not carry it. Not supported: Q9VB70
      (Lateral signaling target protein 2 homolog); B4G2G5 (Lateral signaling target protein 2 homolog); B4IC49
      (Lateral signaling target protein 2 homolog); B4JHI7 (Lateral signaling target protein 2 homolog); Q7QAJ2
      (Lateral signaling target protein 2 homolog); B3MT31 (Lateral signaling target protein 2 homolog); and others.
      UniProtKB entries matching: 3192. The 13 unsupported entries are insect Lateral signaling target protein 2
      (Lst2) homologues, FYVE-domain proteins without a myotubularin phosphatase domain. Of the 3192 UniProtKB matches,
      126 lack InterPro IPR010569 (Myotubularin-like, phosphatase domain).'
  go_annotations:
  - go_id: GO:0004438
    go_label: phosphatidylinositol-3-phosphate phosphatase activity
    aspect: MF
  entries:
  - id: 2.30.29.30:FF:000038
    type: FUNFAM
    label: Myotubularin 1, isoform CRA_a
    appears_in_condition_sets:
    - 1
    protein_count: 15
    related_entries:
    - relationship: EQUIV
      target_id: 3.30.40.10:FF:000073
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 15
    - relationship: EQUIV
      target_id: IPR039802
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 15
    - relationship: EQUIV
      target_id: IPR046352
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 15
    - relationship: PREDICTS
      target_id: GO:0004438
      containment: 1.0
      jaccard_similarity: 0.185
      intersection_count: 15
      exclusive_count: 0
  - id: 3.30.40.10:FF:000073
    type: FUNFAM
    label: myotubularin-related protein 4 isoform X2
    appears_in_condition_sets:
    - 2
    protein_count: 19
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.29.30:FF:000038
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: EQUIV
      target_id: IPR039802
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 19
    - relationship: PREDICTED_BY
      target_id: IPR046352
      containment: 1.0
      jaccard_similarity: 0.158
      intersection_count: 3
      exclusive_count: 0
    - relationship: PREDICTS
      target_id: GO:0004438
      containment: 1.0
      jaccard_similarity: 0.235
      intersection_count: 19
      exclusive_count: 0
  - id: IPR039802
    type: INTERPRO
    source: ipr2go
    protein_count: 2
    asserted_predicted_go_terms:
    - GO:0004438
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.29.30:FF:000038
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: EQUIV
      target_id: 3.30.40.10:FF:000073
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: EQUIV
      target_id: IPR046352
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 2
    - relationship: PREDICTS
      target_id: GO:0004438
      containment: 1.0
      jaccard_similarity: 0.025
      intersection_count: 2
      exclusive_count: 0
  - id: IPR046352
    type: INTERPRO
    source: ipr2go
    protein_count: 3
    asserted_predicted_go_terms:
    - GO:0004438
    related_entries:
    - relationship: EQUIV
      target_id: 2.30.29.30:FF:000038
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 3
    - relationship: PREDICTS
      target_id: 3.30.40.10:FF:000073
      containment: 0.158
      jaccard_similarity: 0.158
      intersection_count: 3
      exclusive_count: 16
    - relationship: EQUIV
      target_id: IPR039802
      containment: 0.0
      jaccard_similarity: 0.0
      intersection_count: 0
      exclusive_count: 3
    - relationship: PREDICTS
      target_id: GO:0004438
      containment: 1.0
      jaccard_similarity: 0.037
      intersection_count: 3
      exclusive_count: 0
  reviewed_protein_count: 0
  unreviewed_protein_count: 0
  created_date: '2023-03-22'
  modified_date: '2025-03-21'
  retrieved_date: '2026-11-09'
  source_condition_set_count: 2
review_summary: 'Both live condition sets were checked against Swiss-Prot. Set 1 is supported: its 5 reviewed matches
  all carry GO:0004438 with non-electronic evidence. Set 2 is not specific to myotubularins. Of its 19 reviewed
  matches, 6 are MTMR3 or MTMR4 experimentally annotated to GO:0004438, for example Q9NYA4 MTMR4 by IDA from PMID:11302699, and 13 are
  insect Lst2 homologues that have a FYVE domain but no phosphatase domain and carry GO:0004438 only from this rule
  (e.g. Q9VB70, IEA GO_REF:0000117 with ARBA:ARBA00035068). In UniProtKB as a whole, 126 of 3192 matches of set
  2 (3.9%) lack the myotubularin phosphatase domain IPR010569.'
action: MODIFY
action_rationale: Set 2 rests on a FunFam of the FYVE zinc-finger region, which MTMR3 and MTMR4 share with unrelated
  FYVE proteins. The rule therefore assigns a phosphatase activity to Lst2 homologues that have no phosphatase domain.
  Set 1 is sound.
suggested_modifications:
- Add InterPro IPR010569 (Myotubularin-like, phosphatase domain) as a required condition of set 2. This keeps 3066
  of the 3192 UniProtKB matches and removes the 126 that lack the phosphatase domain, including the Lst2 homologues.
condition_overlap:
  assessment: NONE
  notes: The two FunFams share no Swiss-Prot protein (intersection 0 in the recorded entries).
taxonomic_scope:
  assessment: TOO_NARROW
  notes: Set 1 is limited to Primates, but all 15 Swiss-Prot members of FunFam 2.30.29.30:FF:000038 in any taxon
    (human, mouse, rat, bovine, chicken, Xenopus, zebrafish, orangutan) carry GO:0004438. The restriction costs
    coverage; it does not cause wrong annotation.
annotation_assessments:
- annotation_kind: GO_TERM
  value: GO:0004438
  label: phosphatidylinositol-3-phosphate phosphatase activity
  assessment: PARTIALLY_CORRECT
  correct_examples:
  - Q13496
  - Q13613
  - Q13614
  - Q13615
  - Q9NYA4
  - Q91XS1
  incorrect_examples:
  - Q9VB70
  - B4G2G5
  - B4IC49
  - B4JHI7
  - Q7QAJ2
  - B3MT31
  - B0WAQ0
  - B3P851
  - B4K982
  - B4PRU6
  - Q17AN2
  - B4M140
  - B4NFJ7
  discriminating_features:
  - InterPro:IPR010569
  notes: 'Correct: Q13615 (MTMR3) GO:0004438 IDA PMID:10900271; Q9NYA4 (MTMR4) GO:0004438 IDA PMID:11302699 and
    PMID:20736309. Incorrect: Q9VB70 (Drosophila Lst2 homologue) GO:0004438 IEA GO_REF:0000117 with ARBA:ARBA00035068;
    its InterPro signatures (IPR000306, IPR011011, IPR013083, IPR017455, IPR043269, IPR051118, IPR063883) are FYVE
    zinc-finger and LST2 entries, with no IPR010569; PANTHER PTHR46465 LATERAL SIGNALING TARGET PROTEIN 2 HOMOLOG.
    Human Lst2 homologue Q9HCC9 is curated as a negative regulator of EGFR signalling. Set 2 in UniProtKB: 3192
    matches, 3066 with IPR010569, 126 without (82 of those in Arthropoda). QuickGO lists 3476 annotations attributed
    to ARBA:ARBA00035068 (2026-11-10).'
confidence: 0.8
corrections:
- date: '2026-11-10'
  withdrawn_claim: The rule lacks safeguards against pseudophosphatase family members that retain the domains but
    lack catalytic activity.
  correction: 'No pseudophosphatase match was shown and none was found. The actual false positives are not myotubularins
    at all: they are FYVE-domain Lst2 homologues matched by the FYVE-region FunFam of set 2.'
  error_type: UNSUPPORTED_SOURCE
  evidence:
  - 'Swiss-Prot matches of CS1: 5 (MTM1, MTMR1, MTMR2), all with non-electronic GO:0004438'
  - 'Swiss-Prot matches of CS2: 6 MTMR3/MTMR4 with non-electronic GO:0004438; 13 Lst2 homologues with GO:0004438
    only from ARBA'
  - 'QuickGO: UniProtKB:Q9VB70 GO:0004438 IEA GO_REF:0000117 with ARBA:ARBA00035068'
- date: '2026-11-10'
  withdrawn_claim: Both FunFams were shown to be 100% contained in GO:0004438 in Swiss-Prot (15 of 15 and 19 of
    19), so the annotation is biochemically accurate for both sets.
  correction: For set 2 the 19 of 19 figure counted the annotations this rule itself places on Swiss-Prot entries.
    Excluding ARBA-derived evidence, 6 of 19 are supported.
  error_type: SAMPLE_OVERGENERALISED
  evidence:
  - 'UniProtKB query xref:"funfam-3.30.40.10:FF:000073" AND taxonomy_id:2759 AND reviewed:true (2026-11-09): 19
    entries; 6 with GO:0004438 by non-IEA evidence, 13 with GO:0004438 only as IEA:UniProtKB-ARBA'
- date: '2026-11-10'
  withdrawn_claim: The Primates restriction on set 1 is arbitrary and an inconsistency that should be harmonised
    with set 2.
  correction: A narrower taxon than necessary limits coverage but does not make any annotation wrong, and the two
    sets use different signatures, so they need not share a taxon.
  error_type: LOW_RECALL_IS_NOT_WRONG
  evidence:
  - 'UniProtKB query xref:"funfam-2.30.29.30:FF:000038" AND reviewed:true: 15 entries, all with GO:0004438; 5 of
    them in Primates'