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EP400 (E1A binding protein p400)

Identity

Other namesCAGH32
E1A binding protein p400
hDomino
p400
TNRC12
HGNC (Hugo) EP400
LocusID (NCBI) 57634
Location 12q24.33
Location_base_pair Starts at 132434465 and ends at 132565011 bp from pter ( according to hg19-Feb_2009)  [Mapping]

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

    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.
      

    Other Solid tumors implicated (Data extracted from papers in the Atlas)

    Solid Tumors AmeloblastomID5945

    External links

    Nomenclature
    HGNC (Hugo)EP400   11958
    Cards
    AtlasEP400ID40457ch12q24
    Entrez_Gene (NCBI)EP400  57634  E1A binding protein p400
    GeneCards (Weizmann)EP400
    Ensembl (Hinxton)ENSG00000183495 [Gene_View]  chr12:132434465-132565011 [Contig_View]  EP400 [Vega]
    ICGC DataPortalENSG00000183495
    AceView (NCBI)EP400
    Genatlas (Paris)EP400
    WikiGenes57634
    SOURCE (Princeton)NM_015409
    Genomic and cartography
    GoldenPath (UCSC)EP400  -  12q24.33   chr12:132434465-132565011 +  12q24.33   [Description]    (hg19-Feb_2009)
    EnsemblEP400 - 12q24.33 [CytoView]
    Mapping of homologs : NCBIEP400 [Mapview]
    OMIM606265   
    Gene and transcription
    Genbank (Entrez)AB040931 AB058721 AK025040 AK074395 AK096311
    RefSeq transcript (Entrez)NM_015409
    RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NT_029419 NW_001838066 NW_004929386
    Consensus coding sequences : CCDS (NCBI)EP400
    Cluster EST : UnigeneHs.723478 [ NCBI ]
    CGAP (NCI)Hs.723478
    Alternative Splicing : Fast-db (Paris)GSHG0007142
    Alternative Splicing GalleryENSG00000183495
    Gene ExpressionEP400 [ NCBI-GEO ]     EP400 [ SEEK ]   EP400 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ96L91 (Uniprot)
    NextProtQ96L91  [Medical]
    With graphics : InterProQ96L91
    Splice isoforms : SwissVarQ96L91 (Swissvar)
    Catalytic activity : Enzyme3.6.4.- [ Enzyme-Expasy ]   3.6.4.-3.6.4.- [ IntEnz-EBI ]   3.6.4.- [ BRENDA ]   3.6.4.- [ KEGG ]   
    Domaine pattern : Prosite (Expaxy)HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)    HSA (PS51204)    MYB_LIKE (PS50090)   
    Domains : Interpro (EBI)HAS_subgr    Helicase/SANT-assoc_DNA-bd    Helicase_ATP-bd    Helicase_C    Myb-like_dom    P-loop_NTPase    SANT/Myb    SNF2_N   
    Related proteins : CluSTrQ96L91
    Domain families : Pfam (Sanger)Helicase_C (PF00271)    HSA (PF07529)    SNF2_N (PF00176)   
    Domain families : Pfam (NCBI)pfam00271    pfam07529    pfam00176   
    Domain families : Smart (EMBL)DEXDc (SM00487)  HSA (SM00573)  SANT (SM00717)  
    DMDM Disease mutations57634
    Blocks (Seattle)Q96L91
    Human Protein AtlasENSG00000183495
    Peptide AtlasQ96L91
    HPRD09378
    IPIIPI00167535   IPI00064931   IPI00783692   IPI00798339   IPI00878154   
    Protein Interaction databases
    DIP (DOE-UCLA)Q96L91
    IntAct (EBI)Q96L91
    FunCoupENSG00000183495
    BioGRIDEP400
    IntegromeDBEP400
    STRING (EMBL)EP400
    Ontologies - Pathways
    QuickGOQ96L91
    Ontology : AmiGOSwr1 complex  DNA binding  chromatin binding  helicase activity  ATP binding  nucleoplasm  chromatin organization  nuclear speck  NuA4 histone acetyltransferase complex  histone H4 acetylation  histone H2A acetylation  
    Ontology : EGO-EBISwr1 complex  DNA binding  chromatin binding  helicase activity  ATP binding  nucleoplasm  chromatin organization  nuclear speck  NuA4 histone acetyltransferase complex  histone H4 acetylation  histone H2A acetylation  
    REACTOMEQ96L91 [protein]
    REACTOME PathwaysREACT_120956 Cellular responses to stress [pathway]
    REACTOME PathwaysREACT_172623 Chromatin organization [pathway]
    REACTOME PathwaysREACT_197818 Chromatin organization [pathway]
    Protein Interaction DatabaseEP400
    Wikipedia pathwaysEP400
    Gene fusion - rearrangments
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)EP400
    SNP (GeneSNP Utah)EP400
    SNP : HGBaseEP400
    Genetic variants : HAPMAPEP400
    1000_GenomesEP400 
    ICGC programENSG00000183495 
    CONAN: Copy Number AnalysisEP400 
    Somatic Mutations in Cancer : COSMICEP400 
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    DECIPHER (Syndromes)12:132434465-132565011
    Mutations and Diseases : HGMDEP400
    OMIM606265   
    MedgenEP400
    GENETestsEP400
    Disease Genetic AssociationEP400
    Huge Navigator EP400 [HugePedia]  EP400 [HugeCancerGEM]
    Genomic VariantsEP400  EP400 [DGVbeta]
    Exome VariantEP400
    dbVarEP400
    ClinVarEP400
    snp3D : Map Gene to Disease57634
    General knowledge
    Homologs : HomoloGeneEP400
    Homology/Alignments : Family Browser (UCSC)EP400
    Phylogenetic Trees/Animal Genes : TreeFamEP400
    Chemical/Protein Interactions : CTD57634
    Chemical/Pharm GKB GenePA27808
    Clinical trialEP400
    Cancer Resource (Charite)ENSG00000183495
    Other databases
    Probes
    Litterature
    PubMed55 Pubmed reference(s) in Entrez
    CoreMineEP400
    GoPubMedEP400
    iHOPEP400

    Bibliography

    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
     
    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
     
    Large-scale characterization of HeLa cell nuclear phosphoproteins.
    Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villˆ©n 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
     
    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
     
    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 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
     
    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, Gˆ§ken J, Farzaneh F, Tavassoli M
    Oncogene. 2007 ; 26 (48) : 6863-6874.
    PMID 17486071
     
    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
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    Contributor(s)

    Written06-2007Sandrine Tyteca
    Chromatin and Cell Proliferation group, LBCMCP-UMR 5088 CNRS, Universite Paul Sabatier, Bat 4R3B1, 118 route de Narbonne, 31062 Toulouse Cedex 9, France

    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 online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/EP400ID40457ch12q24.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Sat Nov 8 16:33:09 CET 2014

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