Transformation/transcription domain-associated protein

TRRAP
Identifiers
Aliases	TRRAP, PAF350/400, PAF400, STAF40, TR-AP, Tra1, transformation/transcription domain associated protein
External IDs	MGI: 2153272 HomoloGene: 39246 GeneCards: TRRAP
Gene location (Human) Chr. Chromosome 7 (human)[1] Band No data available Start 98,877,933 bp[1] End 99,013,243 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band No data available Start 144,767,732 bp[2] End 144,859,778 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transcription cofactor activity • protein binding • thiol-dependent ubiquitinyl hydrolase activity • kinase activity Cellular component • Golgi apparatus • transcription factor TFTC complex • STAGA complex • NuA4 histone acetyltransferase complex • nucleoplasm • PCAF complex • nucleus • Swr1 complex • histone acetyltransferase complex Biological process • regulation of transcription, DNA-templated • histone H2A acetylation • transcription, DNA-templated • histone deubiquitination • histone H4 acetylation • phosphorylation • beta-catenin-TCF complex assembly • histone acetylation • covalent chromatin modification • protein deubiquitination • DNA repair Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8295	100683
Ensembl	ENSG00000196367	ENSMUSG00000045482
UniProt	Q9Y4A5	Q80YV3
RefSeq (mRNA)	NM_003496 NM_001244580	NM_001081362
RefSeq (protein)	NP_001231509 NP_003487	n/a
Location (UCSC)	Chr 7: 98.88 – 99.01 Mb	Chr 7: 144.77 – 144.86 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Transformation/transcription domain-associated protein, also known asTRRAP, is a protein that in humans is encoded by the TRRAP gene.^[5][6] TRRAP belongs to the phosphatidylinositol 3-kinase-related kinase protein family.

Function

TRRAP is an adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which in turn is responsible for epigenetic transcription activation. TRRAP has a central role in MYC (c-Myc) transcription activation, and also participates in cell transformation by MYC. It is required for p53/TP53-, E2F1-, and E2F4-mediated transcription activation. It is also involved in transcription activation mediated by the adenovirus E1A, a viral oncoprotein that deregulates transcription of key genes.^[7]

TRRAP is also required for the mitotic checkpoint and normal cell cycle progression. The MRN complex (composed of MRE11, RAD50, and NBS1) is involved in the detection and repair of DNA double-strand breaks (DSBs). TRRAP associates with the MRN complex and when TRRAP is removed, the complex shows reduced cDNA end-joining activity. Hence, TRRAP may function as a link between DSB repair and chromatin remodeling.^[8][9]

Model organisms

Model organisms have been used in the study of TRRAP function. A conditional knockout mouse line, called Trrap^{tm1a(EUCOMM)Wtsi[15][16]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[17][18][19]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[13][20] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed.^[13] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.^[13]

Interactions

Transformation/transcription domain-associated protein has been shown to interact with:

• ACTL6A,^[21]
• EP400,^[22]
• MAX,^[5][23]
• Myc,^{[5][21][23][24]}
• PCAF,^[22][24]
• SUPT3H,^[25] and
• TAF9.^[25] and

References

Further reading