TRRAP

TRRAP, or Transformation/Transcription domain-associated protein, is a large nuclear protein encoded by the human TRRAP gene. It is the vertebrate homolog of the yeast Tra1 protein and acts as a core component of the SAGA (Spt-Ada-Gcn5 acetyltransferase) coactivator complex, as well as related complexes such as TFTC-TREX-2. The protein features a domain architecture that includes an N-terminal scaffold region and a central PI3K-related kinase–like domain that is generally considered catalytically inactive, classifying TRRAP as a pseudokinase. This domain is thought to mediate protein–protein interactions rather than phosphorylate substrates.

Functionally, TRRAP serves as a scaffolding subunit that helps assemble transcriptional activator complexes and recruits histone acetyltransferases to gene promoters. By anchoring these enzymatic modules, TRRAP facilitates chromatin modification and transcriptional initiation in response to cellular signals, linking signaling pathways to gene expression programs.

TRRAP engages with major transcriptional regulators such as c-Myc, p53, and E2F family members, supporting expression programs involved in cell growth, DNA damage responses, and cell-cycle control. In cells lacking TRRAP, transcriptional activation by these factors can be impaired, and cellular proliferation may be affected, reflecting its essential role in transcriptional regulation.

Biological and clinical notes indicate that TRRAP is essential for development in model organisms and is broadly conserved across eukaryotes. In humans, it is a key component of multiple coactivator complexes, and alterations in its expression or function have been observed in various cancer contexts, illustrating its role in controlling growth-related transcriptional programs. TRRAP is not an enzyme but functions primarily as a structural scaffold within chromatin-modifying assemblies.