EP400 (E1A binding protein p400)

2007-06-01   Sandrine Tyteca 

Chromatin, Cell Proliferation group, LBCMCP-UMR 5088 CNRS, Universite Paul Sabatier, Bat 4R3B1, 118 route de Narbonne, 31062 Toulouse Cedex 9, France





The EP400 gene consists of 52 exons and spans 130.5 kb of genomic sequence on chromosome 12.


The predominant mRNA transcribed from this gene is 12,265 nt long. This is actually the isoform 2 of EP400.
Three other isoforms generated by alternative splicing have been described :
  • Isoform 1 retains an alternatively spliced sequence inside intron 2.
  • Isoform 3 lacks exon 4.
  • Isoform 4 lacks exon 23.
  • Pseudogene

    There is an EP400 pseudogene termed "EP400 N-terminal like" (EP400-NL) in the same locus.


    Atlas Image


    The EP400 protein (isoform 2) is 3124 amino acids long and its molecular weight is about 400 kDa. It was cloned and characterized in 2001 thanks to its interation with the E1A oncoprotein.
  • Isoform 1 produces a 3160 aa long protein.
  • Isoform 3 produces a 3087 aa long protein.
  • Isoform 4 produces a 3043 aa long protein.
    There has been no experimental confirmation for isoforms 3 and 4.
    The only described post-translational modification is a phosphorylation on Ser736.
  • Expression

    No data.


    EP400 belongs to chromatin remodelling complexes which are located in the nucleus, so it is probably nuclear. However, its cellular localization has not been formally monitored to date.


    EP400 belongs to the SWI2/SNF2 family of ATPases and is found in two highly related chromatin remodelling complexes : the Tip60 and p400 complexes. In these complexes, EP400 is associated with other enzymes such as the Tip60 histone acetyltransferase and/or the RuvBL1 and RuvBL2 helicases. (Note : putative specific functions of each splicing variant have not been investigated to date)

  • Functions at the cellular level :
    EP400 has been implicated in cell cycle control, apoptosis and development.
    First, the depletion of EP400 in untransformed human fibroblasts leads to senescence through induction of the p53-p21 pathway. Likewise, the EP400 knock-down induces a p21-dependent cell cycle arrest in human cell lines. According to these results, EP400 seems to favour cell proliferation.
    On the other hand, EP400 is required for E1A-mediated apoptosis. Similarly, EP400 is required for apoptosis upon DNA damage in human cell lines. Thus, EP400 also favours apoptosis, possibly through preventing cell cycle arrest.
    Finally, the murine homolog of EP400 appears to be involved in embryonic hematopoiesis.

  • Functions at the molecular level :
    EP400 has ATP-dependent chromatin remodelling activity. Accordingly, EP400 was shown to be recruited along with the Tip60 complex on promoters by the c-myc and E2F transcription factors. Moreover, the EP400 homolog in drosophila is able to exchange specific histone variants at double-strand breaks.
  • Homology

    EP400 contains the SNF2 N-terminal domain shared by all ATPases of the SWI2/SNF2 family (SNF2, STH1, RAD16, RAD54, ISWI...). It also bears helicase-specific domains (see diagram):
  • an helicase C-terminal domain
  • an HSA domain
  • a DEXH box which contains the ATP-binding region.

    Putative homologs in other species (non exhaustive) :

  • M.musculus : Ep400
  • R.norvegicus : Ep400
  • G.gallus : EP400
  • D.melanogaster : DOM or domino
  • Implicated in

    Entity name
    It was shown that EP400 is a target for the E1A viral oncoprotein transforming activity.
    Indeed, studies showed that the overexpression of specific EP400 fragments corresponding to the E1A binding region (the SWI2/SNF2 domain) enhance the ability of E1A to transform rat embryo fibroblasts in the presence of ras. Moreover, the same fragments are able to partially restore the transforming activity of a tranformation-defective E1A mutant.


    Pubmed IDLast YearTitleAuthors
    153029352004Large-scale characterization of HeLa cell nuclear phosphoproteins.Beausoleil SA et al
    156551092005The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway.Chan HM et al
    174860712007p400 function is required for the adenovirus E1A-mediated suppression of EGFR and tumour cell killing.Flinterman MB et al
    127761772003MYC recruits the TIP60 histone acetyltransferase complex to chromatin.Frank SR et al
    115091792001The p400 complex is an essential E1A transformation target.Fuchs M et al
    155284082004Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions.Kusch T et al
    157411652005p400 is required for E1A to promote apoptosis.Samuelson AV et al
    166016862006Tip60 and p400 are both required for UV-induced apoptosis but play antagonistic roles in cell cycle progression.Tyteca S et al
    175352492007Critical role of the p400/mDomino chromatin-remodeling ATPase in embryonic hematopoiesis.Ueda T et al

    Other Information

    Locus ID:

    NCBI: 57634
    MIM: 606265
    HGNC: 11958
    Ensembl: ENSG00000183495


    dbSNP: 57634
    ClinVar: 57634
    TCGA: ENSG00000183495
    COSMIC: EP400


    Gene IDTranscript IDUniprot

    Expression (GTEx)



    PathwaySourceExternal ID
    Cellular responses to stressREACTOMER-HSA-2262752
    Cellular SenescenceREACTOMER-HSA-2559583
    DNA Damage/Telomere Stress Induced SenescenceREACTOMER-HSA-2559586
    Formation of Senescence-Associated Heterochromatin Foci (SAHF)REACTOMER-HSA-2559584
    Chromatin organizationREACTOMER-HSA-4839726
    Chromatin modifying enzymesREACTOMER-HSA-3247509
    HATs acetylate histonesREACTOMER-HSA-3214847

    Protein levels (Protein atlas)

    Not detected


    Pubmed IDYearTitleCitations
    208762832010The p400 ATPase regulates nucleosome stability and chromatin ubiquitination during DNA repair.90
    189851552008Analysis of Myc-induced histone modifications on target chromatin.58
    156551092005The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway.54
    191692792009The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways.38
    166016862006Tip60 and p400 are both required for UV-induced apoptosis but play antagonistic roles in cell cycle progression.37
    232669552012The chromatin remodeler p400 ATPase facilitates Rad51-mediated repair of DNA double-strand breaks.31
    266692632016EP400 Deposits H3.3 into Promoters and Enhancers during Gene Activation.24
    157411652005p400 is required for E1A to promote apoptosis.22
    203511802010The SANT domain of p400 ATPase represses acetyltransferase activity and coactivator function of TIP60 in basal p21 gene expression.20
    243325722014A blood-based three-gene signature for the non-invasive detection of early human hepatocellular carcinoma.20


    Sandrine Tyteca

    EP400 (E1A binding protein p400)

    Atlas Genet Cytogenet Oncol Haematol. 2007-06-01

    Online version: http://atlasgeneticsoncology.org/gene/40457/ep400-(e1a-binding-protein-p400)