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E2F6 (E2F transcription factor 6)

Written2004-03Matthew Oberley
McArdle Laboratory for Cancer Research, University of Wisconsin - Madison, 1400 University Ave. Madison, WI 53706, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)E2F-6
HGNC (Hugo) E2F6
LocusID (NCBI) 1876
Atlas_Id 521
Location 2p25.1  [Link to chromosome band 2p25]
Location_base_pair Starts at 11584501 and ends at 11606303 bp from pter ( according to hg19-Feb_2009)  [Mapping E2F6.png]
Fusion genes
(updated 2016)
E2F6 (2p25.1) / HLA-DRB1 (6p21.32)E2F6 (2p25.1) / LYRM4 (6p25.1)E2F6 (2p25.1) / PDIA6 (2p25.1)
GREB1 (2p25.1) / E2F6 (2p25.1)

DNA/RNA

Description In humans, E2F6 has 8 exons that span 20881 bp of genomic sequence. It has an ORF of 843 nt.
Transcription There have been 5 mRNA splice variants identified in humans.
  • Transcript variant 1 is the predominant transcript, and it encodes the longest mRNA isoform (a), which is 2342 bp.
  • Transcript variant 2 contains an additional segment (2413 bp mRNA), compared to variant 1, that causes a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform b) is much shorter than isoform a. Transcript variants 2 and 4 encode isoform b.
  • Transcript variant 3 lacks a segment (2287 bp mRNA), compared to variant 1, that causes a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform c) is much shorter than isoform a.
  • Transcript variant 4 contains two additional segments (2546 bp mRNA), compared to variant 1, that cause a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform b) is much shorter than isoform a.
  • Transcript variant 5 contains an additional segment (2475 bp mRNA), compared to variant 1, that causes a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform d) is much shorter than isoform a.
  • Pseudogene There is an E2F6 pseudogene located on chromosome 22q11.2 (LOC376818) containing 2144 bp of the E2F6 gene with no introns.

    Protein

     
      Diagram created by M. Oberley.
    Description The predominately expressed isoform is 282 amino acids, and is . The DNA binding domain is thought to be between aa 50 and 129. It has a DEF box between aa 95 to 195. The dimerization domain is thought to reside between aa 130 and 222. There is a leucine zipper domain between aa 143 and 164. The transcriptional repression domain is located on the C terminus from aa 173 to 281. The N-terminal 1-75 aa are missing in isoform B which is predicted to be 206 AA.
    Expression Ubiquitous, though more highly expressed in the placenta, skeletal muscle, heart, ovary, kidney, small intestine and spleen.
    Localisation Nuclear
    Function Heterodimerization with DP1 or 2 creates a sequence specific transcriptional repressor. Overexpression of E2F6 can delay the exit of cells from S-phase, indicating a role for E2F6 in cell-cycle control. E2F6 has been shown via yeast two hybrid and co-IPs to interact with members of the polycomb repressive complex 1, such as Bmi1, RYBP, RING1, MEL-18, and Mph1. The functional outcome of these interactions are as of yet unclear. E2F6 has been biochemically purified in a complex containing polycomb group members h-1(3) mbt like protein, RING1, RING2, hMBLR, as well as YAF and HP1g; this complex also contained a novel euchromatic histone methyltransferase (Eu-HMTase1). This finding led to speculation that E2F6 controlled cellular entry into quiescence, but E2F6 nullizygous MEFs had no kinetic changes or defects in their ability to enter quiescence, or to re-enter into the cell-cycle. However, these animals had homeotic transformations of the axial skeleton, a phenotype that resembled Bmi1 nullizygous mice. This implicated E2F6 in regulation of normal development.
    Homology E2F6 has homology with E2Fs1-5 in the DNA-binding domain, the dimerization domain, and the marked box domain located between aa 231 and 239.

    Mutations

    Note A synthetic mutation in aa 68; L->E: reduced E2F6 transcriptional repressor activity by abrogating DNA binding, but had little effect on S-phase entry.

    Implicated in

    Note
      
    Entity Development
    Note E2F6 is required for normal homeotic development in murine models as mice nullizygous for E2F6 display transformations in the axial skeleton.
    Disease None known.
      

    Bibliography

    Dynamic recruitment of NF-Y and histone acetyltransferases on cell-cycle promoters.
    Caretti G, Salsi V, Vecchi C, Imbriano C, Mantovani R
    The Journal of biological chemistry. 2003 ; 278 (33) : 30435-30440.
    PMID 12771133
     
    E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription.
    Cartwright P, Müller H, Wagener C, Holm K, Helin K
    Oncogene. 1998 ; 17 (5) : 611-623.
    PMID 9704927
     
    Two different E2F6 proteins generated by alternative splicing and internal translation initiation.
    Dahme T, Wood J, Livingston DM, Gaubatz S
    European journal of biochemistry / FEBS. 2002 ; 269 (20) : 5030-5036.
    PMID 12383262
     
    Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6.
    Gaubatz S, Wood JG, Livingston DM
    Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (16) : 9190-9195.
    PMID 9689056
     
    Molecular cloning and characterization of the mouse E2F6 gene.
    Kherrouche Z, Begue A, Stehelin D, Monté D
    Biochemical and biophysical research communications. 2001 ; 288 (1) : 22-33.
    PMID 11594747
     
    An E2F-like repressor of transcription.
    Morkel M, Wenkel J, Bannister AJ, Kouzarides T, Hagemeier C
    Nature. 1997 ; 390 (6660) : 567-568.
    PMID 9403682
     
    E2F6 negatively regulates BRCA1 in human cancer cells without methylation of histone H3 on lysine 9.
    Oberley MJ, Inman DR, Farnham PJ
    The Journal of biological chemistry. 2003 ; 278 (43) : 42466-42476.
    PMID 12909625
     
    A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells.
    Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y
    Science (New York, N.Y.). 2002 ; 296 (5570) : 1132-1136.
    PMID 12004135
     
    Homeotic transformations of the axial skeleton that accompany a targeted deletion of E2f6.
    Storre J, Elsässer HP, Fuchs M, Ullmann D, Livingston DM, Gaubatz S
    EMBO reports. 2002 ; 3 (7) : 695-700.
    PMID 12101104
     
    Sibling rivalry in the E2F family.
    Trimarchi JM, Lees JA
    Nature reviews. Molecular cell biology. 2002 ; 3 (1) : 11-20.
    PMID 11823794
     

    Citation

    This paper should be referenced as such :
    Oberley, M
    E2F6 (E2F transcription factor 6)
    Atlas Genet Cytogenet Oncol Haematol. 2004;8(2):63-64.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/E2F6ID521.html


    External links

    Nomenclature
    HGNC (Hugo)E2F6   3120
    Cards
    AtlasE2F6ID521
    Entrez_Gene (NCBI)E2F6  1876  E2F transcription factor 6
    AliasesE2F-6
    GeneCards (Weizmann)E2F6
    Ensembl hg19 (Hinxton)ENSG00000169016 [Gene_View]  chr2:11584501-11606303 [Contig_View]  E2F6 [Vega]
    Ensembl hg38 (Hinxton)ENSG00000169016 [Gene_View]  chr2:11584501-11606303 [Contig_View]  E2F6 [Vega]
    ICGC DataPortalENSG00000169016
    TCGA cBioPortalE2F6
    AceView (NCBI)E2F6
    Genatlas (Paris)E2F6
    WikiGenes1876
    SOURCE (Princeton)E2F6
    Genetics Home Reference (NIH)E2F6
    Genomic and cartography
    GoldenPath hg19 (UCSC)E2F6  -     chr2:11584501-11606303 -  2p25.1   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)E2F6  -     2p25.1   [Description]    (hg38-Dec_2013)
    EnsemblE2F6 - 2p25.1 [CytoView hg19]  E2F6 - 2p25.1 [CytoView hg38]
    Mapping of homologs : NCBIE2F6 [Mapview hg19]  E2F6 [Mapview hg38]
    OMIM602944   
    Gene and transcription
    Genbank (Entrez)AF041381 AF059292 AF088059 AK096197 AK223159
    RefSeq transcript (Entrez)NM_001278275 NM_001278276 NM_001278277 NM_001278278 NM_198256 NM_198257 NM_198258 NM_198325 NM_212540
    RefSeq genomic (Entrez)NC_000002 NC_018913 NT_005334 NW_004929298
    Consensus coding sequences : CCDS (NCBI)E2F6
    Cluster EST : UnigeneHs.603093 [ NCBI ]
    CGAP (NCI)Hs.603093
    Alternative Splicing GalleryENSG00000169016
    Gene ExpressionE2F6 [ NCBI-GEO ]   E2F6 [ EBI - ARRAY_EXPRESS ]   E2F6 [ SEEK ]   E2F6 [ MEM ]
    Gene Expression Viewer (FireBrowse)E2F6 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)1876
    GTEX Portal (Tissue expression)E2F6
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtO75461   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtO75461  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProO75461
    Splice isoforms : SwissVarO75461
    PhosPhoSitePlusO75461
    Domains : Interpro (EBI)E2F    E2F_CC-MB    E2F_WHTH_DNA-bd_dom    Transcription_factor_E2F6    WHTH_DNA-bd_dom   
    Domain families : Pfam (Sanger)E2F_CC-MB (PF16421)    E2F_TDP (PF02319)   
    Domain families : Pfam (NCBI)pfam16421    pfam02319   
    Conserved Domain (NCBI)E2F6
    DMDM Disease mutations1876
    Blocks (Seattle)E2F6
    SuperfamilyO75461
    Human Protein AtlasENSG00000169016
    Peptide AtlasO75461
    HPRD04251
    IPIIPI00289560   IPI01011061   IPI00893548   IPI00414333   IPI00386595   IPI00893672   IPI00894414   
    Protein Interaction databases
    DIP (DOE-UCLA)O75461
    IntAct (EBI)O75461
    FunCoupENSG00000169016
    BioGRIDE2F6
    STRING (EMBL)E2F6
    ZODIACE2F6
    Ontologies - Pathways
    QuickGOO75461
    Ontology : AmiGOregulation of transcription involved in G1/S transition of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription corepressor activity  protein binding  nucleus  transcription factor complex  transcription, DNA-templated  MLL1 complex  
    Ontology : EGO-EBIregulation of transcription involved in G1/S transition of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription corepressor activity  protein binding  nucleus  transcription factor complex  transcription, DNA-templated  MLL1 complex  
    NDEx NetworkE2F6
    Atlas of Cancer Signalling NetworkE2F6
    Wikipedia pathwaysE2F6
    Orthology - Evolution
    OrthoDB1876
    GeneTree (enSembl)ENSG00000169016
    Phylogenetic Trees/Animal Genes : TreeFamE2F6
    HOVERGENO75461
    HOGENOMO75461
    Homologs : HomoloGeneE2F6
    Homology/Alignments : Family Browser (UCSC)E2F6
    Gene fusions - Rearrangements
    Fusion : MitelmanE2F6/LYRM4 [2p25.1/6p25.1]  
    Fusion : MitelmanGREB1/E2F6 [2p25.1/2p25.1]  [t(2;2)(p25;p25)]  
    Fusion: TCGAE2F6 2p25.1 LYRM4 6p25.1 BRCA
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerE2F6 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)E2F6
    dbVarE2F6
    ClinVarE2F6
    1000_GenomesE2F6 
    Exome Variant ServerE2F6
    ExAC (Exome Aggregation Consortium)E2F6 (select the gene name)
    Genetic variants : HAPMAP1876
    Genomic Variants (DGV)E2F6 [DGVbeta]
    DECIPHER (Syndromes)2:11584501-11606303  ENSG00000169016
    CONAN: Copy Number AnalysisE2F6 
    Mutations
    ICGC Data PortalE2F6 
    TCGA Data PortalE2F6 
    Broad Tumor PortalE2F6
    OASIS PortalE2F6 [ Somatic mutations - Copy number]
    Somatic Mutations in Cancer : COSMICE2F6  [overview]  [genome browser]  [tissue]  [distribution]  
    Mutations and Diseases : HGMDE2F6
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutasearch E2F6
    DgiDB (Drug Gene Interaction Database)E2F6
    DoCM (Curated mutations)E2F6 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)E2F6 (select a term)
    intoGenE2F6
    NCG5 (London)E2F6
    Cancer3DE2F6(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM602944   
    Orphanet
    MedgenE2F6
    Genetic Testing Registry E2F6
    NextProtO75461 [Medical]
    TSGene1876
    GENETestsE2F6
    Huge Navigator E2F6 [HugePedia]
    snp3D : Map Gene to Disease1876
    BioCentury BCIQE2F6
    ClinGenE2F6
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD1876
    Chemical/Pharm GKB GenePA27578
    Clinical trialE2F6
    Miscellaneous
    canSAR (ICR)E2F6 (select the gene name)
    Probes
    Litterature
    PubMed56 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineE2F6
    EVEXE2F6
    GoPubMedE2F6
    iHOPE2F6
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Thu Feb 2 14:00:14 CET 2017

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