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transformation/transcription domain-associated protein; 350/400 kD PCAF-associated factor; PAF350/400; STAF40; tra1 homolog (TRRAP, PAF400)
Function:
- adapter protein
- essential for early development
- required for the mitotic checkpoint & normal cell cycle progression
- 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 & H2A
- role in MYC transcription activation, & participates in cell transformation by MYC
- required for p53/TP53-, E2F1- & E2F4-mediated transcription activation
- probably acts by linking transcription factors such as MYC or E2F1 to HAT complexes such as STAGA thus allowing transcription activation
- probably not required in the steps following histone acetylation in processes of transcription activation
- may be required for the mitotic checkpoint & normal cell cycle progression
- interacts with MYC, E2F1 & E2F4 transcription factors
- interacts directly with p53/TP53
- interacts with GCN5L2
- component of various HAT complexes
- component of the PCAF complex
- component of the TFTC-HAT complex
- component of the NuA4 histone acetyltransferase complex
- component of the STAGA complex
- component of the BAF53 complex
Structure:
- the PI3K/PI4K domain is required for the recruitment of HAT complexes, & the MYC-dependent transactivation
- although strongly related to the PI3/PI4-kinase family, TRRAP lacks typical motifs that constitute the catalytic site of PI3/PI4-kinase proteins, & lacks such activity
- belongs to the PI3/PI4-kinase family, TRA1 subfamily
- contains 1 FAT domain
- contains 1 FATC domain
- contains 1 PI3K/PI4K domain
Compartment: nucleus
Alternative splicing: named isoforms=2
Pathology:
- involved in transcription activation mediated by the adenovirus E1A, a viral oncoprotein that deregulates transcription of key genes
Interactions
molecular events
General
nuclear protein
phosphoprotein
Properties
SIZE: entity length = 3859 aa
MW = 438 kD
COMPARTMENT: cell nucleus
MOTIF: proline-rich region
SITE: 485-526
MOTIF: proline residue (SEVERAL)
Ser phosphorylation site {S1628}
TP53 interaction {2010-2388}
MOTIF: nuclear translocation signal {2047-2062}
Ser phosphorylation site {S2051}
Ser phosphorylation site {S2077}
Thr phosphorylation site {T2333}
Thr phosphorylation site {T2601}
FAT domain
NAME: FAT domain
SITE: 2704-3275
MOTIF: Tyr phosphorylation site
binding site
FOR-BINDING-OF: Paxillin
PI3K/PI4K {3528-3826}
FATC {3827-3859}
Database Correlations
OMIM 603015
UniProt Q9Y4A5
PFAM correlations
Entrez Gene 8295
Kegg hsa:8295
References
- UniProt :accession Q9Y4A5
- OMIM :accession 603015
- Pelengaris S, Khan M, Evan G.
c-MYC: more than just a matter of life and death.
Nat Rev Cancer. 2002 Oct;2(10):764-76. Review.
PMID: 12360279
Component-of
molecular complex