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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | 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. |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | KEEP AS NON CORE | 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. |
| GO:0140861 DNA repair-dependent chromatin remodeling | IBA GO_REF:0000033 | KEEP AS NON CORE | 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. |
| GO:0035267 NuA4 histone acetyltransferase complex | IBA GO_REF:0000033 | ACCEPT | 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. |
| GO:0000124 SAGA complex | IBA GO_REF:0000033 | ACCEPT | 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. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | 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. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | 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. |
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Download this section (compressed HTML)Q: 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?
Experiment: 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.
Experiment: 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.
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