TRRAP
Domain
The PI3K/PI4K domain is required for the recruitment of HAT complexes, and the MYC-dependent transactivation. Although it is strongly related to the PI3/PI4-kinase family, it lacks the typical motifs that constitute the catalytic site of PI3/PI4-kinase proteins, and lacks such activity.
Function
Adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which gives a specific tag for epigenetic transcription activation. Component of the NuA4 histone acetyltransferase complex which is responsible for acetylation of nucleosomal histones H4 and H2A. Plays a central role in MYC transcription activation, and also participates in cell transformation by MYC. Required for p53/TP53-, E2F1- and E2F4-mediated transcription activation. Also involved in transcription activation mediated by the adenovirus E1A, a viral oncoprotein that deregulates transcription of key genes. Probably acts by linking transcription factors such as E1A, MYC or E2F1 to HAT complexes such as STAGA thereby allowing transcription activation. Probably not required in the steps following histone acetylation in processes of transcription activation. May be required for the mitotic checkpoint and normal cell cycle progression. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. May play a role in the formation and maintenance of the auditory system (By similarity).
Involvement in disease
TRRAP mutation Phe-722 has been frequently found in cutaneous malignant melanoma, suggesting that TRRAP may play a role in the pathogenesis of melanoma.
Developmental delay with or without dysmorphic facies and autism
DEDDFA
An autosomal dominant neurodevelopmental disorder apparent from infancy or early childhood. Some patients present with intellectual disability and renal, cardiac, genitourinary systems, as well as structural brain abnormalities. In some cases, the phenotype is less severe, has no systemic involvement and is characterized by autism spectrum disorder and/or intellectual disability, sometimes associated with epilepsy. Affected individuals manifest variable dysmorphic features.
None
The disease is caused by variants affecting the gene represented in this entry.
Deafness, autosomal dominant, 75
DFNA75
A form of non-syndromic deafness characterized by late-onset hearing loss that involves mid and high frequencies, and progresses to encompass all frequencies.
None
The disease may be caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the PI3/PI4-kinase family. TRA1 subfamily.
Cellular localization
- Nucleus
Alternative names
PAF400, TRRAP, Transformation/transcription domain-associated protein, 350/400 kDa PCAF-associated factor, STAF40, Tra1 homolog, PAF350/400