trr-1

id: A8WTE8
gene_symbol: trr-1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:6238
  label: Caenorhabditis briggsae
description: >-
  Cbr-TRR-1 is the Caenorhabditis briggsae ortholog of TRRAP (yeast Tra1), a very large
  (~4115 aa) member of the phosphatidylinositol 3-kinase-related kinase (PIKK) superfamily.
  Despite containing the canonical PIKK architecture (HEAT/TPR solenoid, FAT domain,
  PI3K/PI4K-like catalytic domain, and FATC domain), it belongs to the TRRAP/Tra1 subfamily —
  the single catalytically inactive lineage of the otherwise all-kinase PIKK family. By orthology
  to TRRAP/Tra1 (human TRRAP is experimentally shown to lack the catalytic-site motifs and any
  kinase activity), Cbr-TRR-1 is inferred to be a catalytically dead pseudokinase; consistent
  with this, its UniProt/GOA records carry no EC number, catalytic activity, or kinase GO
  annotation. Its
  function is structural: it serves as a large scaffolding subunit that nucleates and stabilizes
  multiprotein histone acetyltransferase (HAT) complexes of the NuA4/TIP60 and SAGA families,
  and helps recruit these complexes to chromatin, thereby contributing to histone acetylation,
  chromatin-based transcriptional coactivation, and DNA-repair-associated chromatin remodeling.
  The protein localizes to the nucleus, including condensed meiotic chromosomes in germ cells.
  In C. briggsae specifically, trr-1 acts downstream of the sex-determination genes tra-2 and
  tra-3 and through the Tip60 HAT complex to control the germline sperm/oocyte fate decision;
  loss-of-function null mutants feminize the germ line (Fog phenotype, producing oocytes instead
  of sperm), and the gene is also required for spermatogenesis and embryonic development.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      TRRAP/Tra1 orthologs act within nuclear chromatin-modifying complexes, and Cbr-TRR-1 is
      documented as nuclear (UniProt subcellular location, with localization to condensed
      chromosomes during meiosis I). Phylogenetic (IBA) assignment of nuclear localization is
      consistent with the experimental and orthology evidence. Accept as a correct, core
      localization for a nuclear HAT-complex scaffold.
    action: ACCEPT
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      TRRAP/Tra1 family members function as scaffolds of SAGA and NuA4/TIP60 coactivator
      complexes and contribute to transcriptional regulation through histone acetylation. The
      IBA assignment is consistent with the family role. The term is correct but fairly general
      (the gene does not itself bind DNA or directly regulate transcription; it does so as a
      structural subunit of HAT coactivators). Keep as a valid but non-core process annotation;
      the core function is the structural/scaffold role within the HAT complex.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0140861
    label: DNA repair-dependent chromatin remodeling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      The NuA4/TIP60 complex, of which TRRAP is the scaffolding subunit, participates in
      chromatin remodeling during the DNA damage response, so phylogenetic propagation of this
      process term is consistent with the ortholog family. There is no C. briggsae-specific
      experimental evidence, but the annotation is biologically plausible and consistent with
      the conserved NuA4/TIP60 role. Keep as a peripheral (non-core) process annotation.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0035267
    label: NuA4 histone acetyltransferase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      TRRAP/Tra1 is a defining scaffolding subunit of the NuA4 (yeast)/TIP60 (metazoan) histone
      acetyltransferase complex, and in C. briggsae trr-1 is reported to act through the Tip60
      HAT complex to control germ-cell fate. The IBA complex membership is well supported by
      orthology and by the gene's documented Tip60-dependent function. Accept as a core
      cellular-component annotation.
    action: ACCEPT
- term:
    id: GO:0000124
    label: SAGA complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      In yeast a single Tra1 protein is shared between NuA4 and SAGA, and in metazoans TRRAP is
      a subunit of SAGA/SAGA-like (STAGA) HAT complexes. Phylogenetic propagation of SAGA complex
      membership to Cbr-TRR-1 is consistent with the conserved family role. There is no
      C. briggsae-specific experimental confirmation, but the assignment is well grounded in the
      ortholog family; accept membership in the SAGA complex.
    action: ACCEPT
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic mapping of the UniProt Subcellular Location keyword (Nucleus) to GO:0005634.
      This is consistent with the experimentally/orthology-supported nuclear localization and
      duplicates the IBA/ISS nucleus annotations. Accept as a correct, redundant localization.
    action: ACCEPT
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Nuclear localization transferred by sequence similarity from the C. elegans ortholog
      (UniProtKB:G5EEV2), which is documented as nuclear with localization to condensed
      chromosomes during meiosis. Consistent with the IBA/IEA nucleus annotations; accept.
    action: ACCEPT
core_functions:
- description: >-
    Structural scaffolding subunit of the NuA4/TIP60 (and SAGA-like) histone acetyltransferase
    complexes. As a catalytically inactive PIKK pseudokinase, Cbr-TRR-1 provides a large
    HEAT/TPR solenoid platform that nucleates assembly and stabilizes these multiprotein HAT
    complexes and aids their recruitment to chromatin, rather than contributing any enzymatic
    (kinase or acetyltransferase) activity itself.
  supported_by:
  - reference_id: GO_REF:0000033
    supporting_text: >-
      IBA annotation places trr-1 as part_of the NuA4 histone acetyltransferase complex,
      consistent with the conserved TRRAP/Tra1 scaffolding role across eukaryotes.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  in_complex:
    id: GO:0035267
    label: NuA4 histone acetyltransferase complex
  locations:
  - id: GO:0005634
    label: nucleus
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      ISS transfer of nuclear localization from the C. elegans ortholog G5EEV2; consistent with
      the UniProt-documented nuclear/condensed-chromosome localization of Cbr-TRR-1.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PANTHER/GO_Central phylogenetic (IBA) inferences for the TRRAP/Tra1 family. The complex
      memberships (NuA4, SAGA), nuclear localization, and chromatin/transcription processes are
      all consistent with the well-characterized conserved scaffolding role of this family.
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Keyword-to-GO mapping of the Nucleus subcellular location; redundant with but consistent
      with the IBA/ISS nucleus annotations.
- id: PMID:24098152
  title: >-
    Evolutionary change within a bipotential switch shaped the sperm/oocyte decision in
    hermaphroditic nematodes.
  findings:
  - statement: >-
      Cbr-TRR-1 acts through the TRA-1 transcription factor to activate Cbr-fog-3 and to control the
      germline sperm/oocyte fate decision; reducing trr-1 activity produces a feminized (Fog) germ line.
    reference_section_type: RESULTS
    supporting_text: >-
      TRR-1 works through TRA-1, both to activate Cbr-fog-3 and to control the sperm/oocyte decision
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Primary functional study for Cbr-trr-1 (Guo, Chen & Ellis, PLoS Genet 2013). Shows trr-1 acts
      through TRA-1 and the Tip60 HAT complex to activate fog-3 and control the germline sperm/oocyte
      fate decision; reduced trr-1 gives a feminized (Fog) germ line, and the gene is required for
      spermatogenesis and embryonic development. Full text is available in the local publications
      cache (content_type: full_text_pdf); the verbatim finding above is quoted directly from it.
suggested_questions:
- question: >-
    Does Cbr-TRR-1 retain any residual catalytic activity, or is its role purely structural, as
    suggested by the loss of canonical PIKK kinase residues in the TRRAP/Tra1 family?
suggested_experiments:
- description: >-
    Affinity-purify Cbr-TRR-1 from C. briggsae germ line and identify co-purifying subunits by
    mass spectrometry to confirm assembly into NuA4/TIP60 and SAGA-like HAT complexes and to map
    germline-specific partners.
- description: >-
    Test whether the Fog phenotype of trr-1 mutants is rescued by a scaffold-competent but
    kinase-domain-mutant transgene, to confirm that the germline sperm/oocyte function depends on
    the structural/scaffolding role rather than any catalytic activity.