ARBA00045851

id: ARBA00045851
description: Assigns a FUNCTION comment describing assembly of a p53/TP53 suppression complex that tethers
  SIRT1 and MDM2, and a possible role in spermatogenesis, to proteins of the MORN repeat-containing protein
  3 family across Eukaryota.
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00045851
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR003409
      label: MORN repeat
    - condition_type: INTERPRO
      value: IPR052472
      label: MORN repeat-containing protein 3
    - condition_type: PANTHER
      value: PTHR46511:SF1
  - number: 2
    conditions:
    - condition_type: FUNFAM
      value: 2.20.110.10:FF:000026
      label: MORN repeat containing 3
    - condition_type: TAXON
      value: Eukaryota
      curie: NCBITaxon:2759
      label: Eukaryota
  go_annotations: []
  entries: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 1802
  created_date: '2024-08-14'
  modified_date: '2025-03-21'
  retrieved_date: '2026-11-10'
  source_condition_set_count: 2
review_summary: 'Both condition sets were read. Set 1 (IPR003409 (MORN repeat) AND IPR052472 (MORN repeat-containing
  protein 3) AND PANTHER:PTHR46511:SF1) has no taxon condition. A query on the PANTHER family (a superset
  of the required subfamily, so an upper bound) returns 1,648 UniProtKB entries (release 2026_04): 874
  vertebrate, 233 arthropod, 75 Viridiplantae and 25 fungal; all 100 plant and fungal entries carry the
  subfamily. The comment the rule assigns names p53/TP53 and MDM2. No Viridiplantae or fungal entry in
  UniProtKB matches the Mdm2/Mdm4 family (IPR016495), and one Viridiplantae and no fungal entry matches
  the p53 family (IPR002117), so in those lineages the text describes partners that are not there. The
  Drosophila entry A1ZB08 carries the comment with evidence ECO:0000256 ARBA:ARBA00045851. The mechanism
  itself was shown for mammalian MORN3 (PMID:29681526), and the spermatogenesis role in mouse (PMID:25248657).'
action: MODIFY
action_rationale: The text is specific to a p53/MDM2 mechanism and the rule applies it to every eukaryotic
  member of the family, including 100 plant and fungal entries whose proteomes have no Mdm2/Mdm4 family
  member. Restricting the rule to the lineage where the mechanism was shown removes those. Whether the
  text holds for non-mammalian animals is not established either way; arthropods do have Mdm2/Mdm4 and
  p53 family members (34 and 653 entries).
suggested_modifications:
- 'Add a taxon condition to set 1 and narrow set 2 from Eukaryota: Mammalia (NCBITaxon:40674), where the
  mechanism was shown, or at most Vertebrata (NCBITaxon:7742).'
- Alternatively keep the scope and reduce the comment to what family membership supports.
taxonomic_scope:
  assessment: TOO_BROAD
  notes: 'Set 1 has no taxon condition and set 2 is limited only to Eukaryota. UniProtKB 2026_04 counts
    for set 1, from a query on the PANTHER family and so upper bounds except where stated: 1,648 entries,
    of which 874 Vertebrata, 233 Arthropoda, 75 Viridiplantae, 25 Fungi. Mdm2/Mdm4 family IPR016495: 2,900
    entries in Vertebrata, 34 in Arthropoda, 0 in Viridiplantae, 0 in Fungi. p53 family IPR002117: 4,674
    in Vertebrata, 653 in Arthropoda, 1 in Viridiplantae, 0 in Fungi.'
annotation_assessments:
- annotation_kind: OTHER
  value: FUNCTION comment
  label: Assembles a suppression complex (suppresome) by tethering SIRT1 and MDM2 to regulate composite
    modifications of p53/TP53
  assessment: PARTIALLY_CORRECT
  matched_protein_count: 1648
  incorrect_protein_count: 100
  incorrect_examples:
  - A0A176VY54
  - A0A0L0S0I5
  - A1ZB08
  notes: 'matched_protein_count is from a query on the PANTHER family PTHR46511, a superset of the subfamily
    PTHR46511:SF1 that set 1 requires, so 1,648 is an upper bound. The plant and fungal counts are exact:
    all 100 of those entries carry PTHR46511:SF1 (UniProtKB 2026_04). incorrect_protein_count is its Viridiplantae
    (75) and Fungi (25) matches, lineages with no Mdm2/Mdm4 family entry (IPR016495) in UniProtKB. A0A176VY54
    (the liverwort Marchantia polymorpha) and A0A0L0S0I5 (the chytrid fungus Allomyces macrogynus) are
    unreviewed entries whose FUNCTION comment is this rule''s text about tethering SIRT1 and MDM2 to p53
    (UniProtKB, 2026-11-10). A1ZB08 (Drosophila melanogaster, unreviewed) also carries the comment with
    ECO:0000256 ARBA:ARBA00045851; it is a weaker case, because arthropods have p53 and Mdm2/Mdm4 family
    members, and is listed as the entry on which the over-annotation was first reported.'
confidence: 0.8
references:
- id: PMID:29681526
  title: A Designed Peptide Targets Two Types of Modifications of p53 with Anti-cancer Activity
  findings:
  - statement: Establishes the MORN3-mediated suppression complex (suppresome) that tethers SIRT1 and
      MDM2 to p53 for deacetylation and ubiquitination
- id: PMID:25248657
  title: Characterization of membrane occupation and recognition nexus repeat containing 3, meiosis expressed
    gene 1 binding partner, in mouse male germ cells
  findings:
  - statement: Mouse MORN3 is involved in regulation of spermatogenesis
- id: PMID:35568981
  title: Membrane occupation and recognition nexus (MORN) motif controls protein localization and function.
  findings:
  - statement: 'Review of MORN motif proteins: the motif contributes to protein localization and function.'
- id: InterPro:IPR052472
  title: MORN repeat-containing protein 3 InterPro entry
  findings:
  - statement: MORN3 assembles suppression complex tethering SIRT1 and MDM2 to p53 for deacetylation and
      ubiquitination
- id: InterPro:IPR003409
  title: MORN repeat InterPro entry
  findings:
  - statement: MORN repeats are lipid-binding modules composed of β-hairpin structures
corrections:
- date: '2026-11-10'
  withdrawn_claim: Drosophila A1ZB08 was flagged in go-annotation#6179 as an inappropriate target because
    the fly gene is not well expressed in testis; a quotation and a reference finding were attributed
    to that issue; confidence 0.4 on a MODIFY verdict.
  correction: The issue could not be read, so the expression claim, the quotation and the finding are
    removed. The scope argument now rests on UniProtKB counts. Confidence is restated as confidence in
    the verdict.
  error_type: UNSUPPORTED_SOURCE
  evidence:
  - A1ZB08 FUNCTION comment carries ECO:0000256 ARBA:ARBA00045851 (UniProtKB, 2026-11-10)
  - '(xref:interpro-IPR003409) AND (xref:interpro-IPR052472) AND (xref:panther-PTHR46511): 1,648 entries;
    75 in taxonomy_id:33090, 25 in taxonomy_id:4751 (UniProtKB 2026_04)'
  - '(xref:interpro-IPR016495) AND (taxonomy_id:33090): 0; AND (taxonomy_id:4751): 0 (UniProtKB 2026_04);
    IPR016495 is "p53 negative regulator Mdm2/Mdm4"'