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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

  1. UniProt :accession Q9Y4A5
  2. OMIM :accession 603015
  3. 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