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EP400 (E1A binding protein p400)

Written2007-06Sandrine Tyteca
Chromatin, Cell Proliferation group, LBCMCP-UMR 5088 CNRS, Universite Paul Sabatier, Bat 4R3B1, 118 route de Narbonne, 31062 Toulouse Cedex 9, France

(Note : for Links provided by Atlas : click)

Identity

Other aliasCAGH32
E1A binding protein p400
hDomino
p400
TNRC12
LocusID (NCBI) 57634
Atlas_Id 40457
Location 12q24.33  [Link to chromosome band 12q24]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ATP2A2 (12q24.11) / EP400 (12q24.33)EP400 (12q24.33) / LMO4 (1p22.3)EP400 (12q24.33) / PHF1 (6p21.32)
EP400 (12q24.33) / SFSWAP (12q24.33)EP400 (12q24.33) / UCP2 (11q13.4)FBRSL1 (12q24.33) / EP400 (12q24.33)
PGAM5 (12q24.33) / EP400 (12q24.33)TRIT1 (1p34.2) / EP400 (12q24.33)YEATS4 (12q15) / EP400 (12q24.33)

DNA/RNA

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

    Protein

     
    Description 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.
    Localisation 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.
    Function 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

    Note
      
    Entity Cancers
    Oncogenesis 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.
      

    Bibliography

    Large-scale characterization of HeLa cell nuclear phosphoproteins.
    Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP
    Proceedings of the National Academy of Sciences of the United States of America. 2004 ; 101 (33) : 12130-12135.
    PMID 15302935
     
    The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway.
    Chan HM, Narita M, Lowe SW, Livingston DM
    Genes & development. 2005 ; 19 (2) : 196-201.
    PMID 15655109
     
    p400 function is required for the adenovirus E1A-mediated suppression of EGFR and tumour cell killing.
    Flinterman MB, Mymryk JS, Klanrit P, Yousef AF, Lowe SW, Caldas C, Gäken J, Farzaneh F, Tavassoli M
    Oncogene. 2007 ; 26 (48) : 6863-6874.
    PMID 17486071
     
    MYC recruits the TIP60 histone acetyltransferase complex to chromatin.
    Frank SR, Parisi T, Taubert S, Fernandez P, Fuchs M, Chan HM, Livingston DM, Amati B
    EMBO reports. 2003 ; 4 (6) : 575-580.
    PMID 12776177
     
    The p400 complex is an essential E1A transformation target.
    Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM
    Cell. 2001 ; 106 (3) : 297-307.
    PMID 11509179
     
    Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions.
    Kusch T, Florens L, Macdonald WH, Swanson SK, Glaser RL, Yates JR 3rd, Abmayr SM, Washburn MP, Workman JL
    Science (New York, N.Y.). 2004 ; 306 (5704) : 2084-2087.
    PMID 15528408
     
    p400 is required for E1A to promote apoptosis.
    Samuelson AV, Narita M, Chan HM, Jin J, de Stanchina E, McCurrach ME, Narita M, Fuchs M, Livingston DM, Lowe SW
    The Journal of biological chemistry. 2005 ; 280 (23) : 21915-21923.
    PMID 15741165
     
    Tip60 and p400 are both required for UV-induced apoptosis but play antagonistic roles in cell cycle progression.
    Tyteca S, Vandromme M, Legube G, Chevillard-Briet M, Trouche D
    The EMBO journal. 2006 ; 25 (8) : 1680-1689.
    PMID 16601686
     
    Critical role of the p400/mDomino chromatin-remodeling ATPase in embryonic hematopoiesis.
    Ueda T, Watanabe-Fukunaga R, Ogawa H, Fukuyama H, Higashi Y, Nagata S, Fukunaga R
    Genes to cells : devoted to molecular & cellular mechanisms. 2007 ; 12 (5) : 581-592.
    PMID 17535249
     

    Citation

    This paper should be referenced as such :
    Tyteca, S
    EP400 (E1A binding protein p400)
    Atlas Genet Cytogenet Oncol Haematol. 2008;12(1):3-4.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/EP400ID40457ch12q24.html


    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 6 ]
      Lung: Translocations in Small Cell Carcinoma
    t(1;12)(p34;q24) TRIT1/EP400
    t(6;12)(p21;q24) EP400/PHF1
    t(12;12)(q15;q24) YEATS4/EP400
    ATP2A2/EP400 (12q24)
    EP400/SFSWAP (12q24)


    External links

    Nomenclature
    Cards
    AtlasEP400ID40457ch12q24.txt
    Aliases
    Genomic and cartography
    Gene and transcription
    RefSeq transcript (Entrez)
    RefSeq genomic (Entrez)
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    BioGPS (Tissue expression)57634
    Protein : pattern, domain, 3D structure
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Protein Interaction databases
    Ontologies - Pathways
    Clinical trials, drugs, therapy
    Miscellaneous
    canSAR (ICR) (select the gene name)
    Probes
    Litterature
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed


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    indexed on : Thu Oct 18 17:35:15 CEST 2018

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