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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

Alias_namesTNRC12
trinucleotide repeat containing 12
Alias_symbol (synonym)CAGH32
KIAA1498
P400
KIAA1818
DKFZP434I225
HGNC (Hugo) EP400
LocusID (NCBI) 57634
Atlas_Id 40457
Location 12q24.33  [Link to chromosome band 12q24]
Location_base_pair Starts at 132434465 and ends at 132565011 bp from pter ( according to hg19-Feb_2009)  [Mapping EP400.png]
Fusion genes
(updated 2016)
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) [ 2 ]
      Soft tissue tumors: an overview
    Lung: Translocations in Small Cell Carcinoma


    External links

    Nomenclature
    HGNC (Hugo)EP400   11958
    Cards
    AtlasEP400ID40457ch12q24
    Entrez_Gene (NCBI)EP400  57634  E1A binding protein p400
    AliasesCAGH32; P400; TNRC12
    GeneCards (Weizmann)EP400
    Ensembl hg19 (Hinxton)ENSG00000183495 [Gene_View]  chr12:132434465-132565011 [Contig_View]  EP400 [Vega]
    Ensembl hg38 (Hinxton)ENSG00000183495 [Gene_View]  chr12:132434465-132565011 [Contig_View]  EP400 [Vega]
    ICGC DataPortalENSG00000183495
    TCGA cBioPortalEP400
    AceView (NCBI)EP400
    Genatlas (Paris)EP400
    WikiGenes57634
    SOURCE (Princeton)EP400
    Genetics Home Reference (NIH)EP400
    Genomic and cartography
    GoldenPath hg19 (UCSC)EP400  -     chr12:132434465-132565011 +  12q24.33   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)EP400  -     12q24.33   [Description]    (hg38-Dec_2013)
    EnsemblEP400 - 12q24.33 [CytoView hg19]  EP400 - 12q24.33 [CytoView hg38]
    Mapping of homologs : NCBIEP400 [Mapview hg19]  EP400 [Mapview hg38]
    OMIM606265   
    Gene and transcription
    Genbank (Entrez)AB040931 AB058721 AK025040 AK074395 AK096311
    RefSeq transcript (Entrez)NM_015409
    RefSeq genomic (Entrez)NC_000012 NC_018923 NT_029419 NW_004929386
    Consensus coding sequences : CCDS (NCBI)EP400
    Cluster EST : UnigeneHs.723478 [ NCBI ]
    CGAP (NCI)Hs.723478
    Alternative Splicing GalleryENSG00000183495
    Gene ExpressionEP400 [ NCBI-GEO ]   EP400 [ EBI - ARRAY_EXPRESS ]   EP400 [ SEEK ]   EP400 [ MEM ]
    Gene Expression Viewer (FireBrowse)EP400 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)57634
    GTEX Portal (Tissue expression)EP400
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ96L91   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ96L91  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ96L91
    Splice isoforms : SwissVarQ96L91
    Catalytic activity : Enzyme3.6.4.- [ Enzyme-Expasy ]   3.6.4.-3.6.4.- [ IntEnz-EBI ]   3.6.4.- [ BRENDA ]   3.6.4.- [ KEGG ]   
    PhosPhoSitePlusQ96L91
    Domaine pattern : Prosite (Expaxy)HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)    HSA (PS51204)    MYB_LIKE (PS50090)   
    Domains : Interpro (EBI)EP400_N    Helicase_ATP-bd    Helicase_C    HSA_dom    Myb-like_dom    P-loop_NTPase    SANT/Myb    SNF2_N   
    Domain families : Pfam (Sanger)EP400_N (PF15790)    Helicase_C (PF00271)    HSA (PF07529)    SNF2_N (PF00176)   
    Domain families : Pfam (NCBI)pfam15790    pfam00271    pfam07529    pfam00176   
    Domain families : Smart (EMBL)DEXDc (SM00487)  HSA (SM00573)  SANT (SM00717)  
    Conserved Domain (NCBI)EP400
    DMDM Disease mutations57634
    Blocks (Seattle)EP400
    SuperfamilyQ96L91
    Human Protein AtlasENSG00000183495
    Peptide AtlasQ96L91
    HPRD09378
    IPIIPI00167535   IPI00064931   IPI00783692   IPI00798339   IPI00878154   
    Protein Interaction databases
    DIP (DOE-UCLA)Q96L91
    IntAct (EBI)Q96L91
    FunCoupENSG00000183495
    BioGRIDEP400
    STRING (EMBL)EP400
    ZODIACEP400
    Ontologies - Pathways
    QuickGOQ96L91
    Ontology : AmiGOSwr1 complex  DNA binding  chromatin binding  helicase activity  protein binding  ATP binding  nucleoplasm  nuclear speck  NuA4 histone acetyltransferase complex  histone H4 acetylation  histone H2A acetylation  protein antigen binding  
    Ontology : EGO-EBISwr1 complex  DNA binding  chromatin binding  helicase activity  protein binding  ATP binding  nucleoplasm  nuclear speck  NuA4 histone acetyltransferase complex  histone H4 acetylation  histone H2A acetylation  protein antigen binding  
    REACTOMEQ96L91 [protein]
    REACTOME PathwaysR-HSA-2559584 Formation of Senescence-Associated Heterochromatin Foci (SAHF) [pathway]
    REACTOME PathwaysR-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence [pathway]
    REACTOME PathwaysR-HSA-3214847 HATs acetylate histones [pathway]
    NDEx NetworkEP400
    Atlas of Cancer Signalling NetworkEP400
    Wikipedia pathwaysEP400
    Orthology - Evolution
    OrthoDB57634
    GeneTree (enSembl)ENSG00000183495
    Phylogenetic Trees/Animal Genes : TreeFamEP400
    HOVERGENQ96L91
    HOGENOMQ96L91
    Homologs : HomoloGeneEP400
    Homology/Alignments : Family Browser (UCSC)EP400
    Gene fusions - Rearrangements
    Fusion : MitelmanATP2A2/EP400 [12q24.11/12q24.33]  [t(12;12)(q24;q24)]  
    Fusion : MitelmanEP400/PHF1 [12q24.33/6p21.32]  [t(6;12)(p21;q24)]  
    Fusion : MitelmanEP400/SFSWAP [12q24.33/12q24.33]  [t(12;12)(q24;q24)]  
    Fusion : MitelmanTRIT1/EP400 [1p34.2/12q24.33]  [t(1;12)(p34;q24)]  
    Fusion : MitelmanYEATS4/EP400 [12q15/12q24.33]  [t(12;12)(q15;q24)]  
    Fusion: TCGAATP2A2 12q24.11 EP400 12q24.33 LUSC
    Fusion: TCGAEP400 12q24.33 SFSWAP 12q24.33 BRCA HNSC LUAD
    Fusion: TCGAYEATS4 12q15 EP400 12q24.33 GBM
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerEP400 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)EP400
    dbVarEP400
    ClinVarEP400
    1000_GenomesEP400 
    Exome Variant ServerEP400
    ExAC (Exome Aggregation Consortium)EP400 (select the gene name)
    Genetic variants : HAPMAP57634
    Genomic Variants (DGV)EP400 [DGVbeta]
    DECIPHER (Syndromes)12:132434465-132565011  ENSG00000183495
    CONAN: Copy Number AnalysisEP400 
    Mutations
    ICGC Data PortalEP400 
    TCGA Data PortalEP400 
    Broad Tumor PortalEP400
    OASIS PortalEP400 [ Somatic mutations - Copy number]
    Somatic Mutations in Cancer : COSMICEP400  [overview]  [genome browser]  [tissue]  [distribution]  
    Mutations and Diseases : HGMDEP400
    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
    BioMutasearch EP400
    DgiDB (Drug Gene Interaction Database)EP400
    DoCM (Curated mutations)EP400 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)EP400 (select a term)
    intoGenEP400
    NCG5 (London)EP400
    Cancer3DEP400(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM606265   
    Orphanet
    MedgenEP400
    Genetic Testing Registry EP400
    NextProtQ96L91 [Medical]
    TSGene57634
    GENETestsEP400
    Huge Navigator EP400 [HugePedia]
    snp3D : Map Gene to Disease57634
    BioCentury BCIQEP400
    ClinGenEP400
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD57634
    Chemical/Pharm GKB GenePA27808
    Clinical trialEP400
    Miscellaneous
    canSAR (ICR)EP400 (select the gene name)
    Probes
    Litterature
    PubMed61 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineEP400
    EVEXEP400
    GoPubMedEP400
    iHOPEP400
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Fri Nov 18 20:00:01 CET 2016

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