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FLASH GENE
Symbol E2F4 contributors: mct - updated : 05-04-2016
HGNC name E2F transcription factor 4, p107/p130-binding
HGNC id 3118
Location 16q22.1      Physical location : 67.226.067 - 67.232.820
Synonym name
  • p107/p130-binding protein
  • E2F transcription factor 4
  • Synonym symbol(s) E2F-4
    DNA
    TYPE functioning gene
    STRUCTURE 6.75 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   triplet
    text structure
  • CAG repeat in exon 7
  • coding region of the E2F4 gene contains a longer spacer segment of a CAG trinucleotide repeat sequence encoding 13 consecutive serine residues, which is highly vulnerable to frameshift mutations in situations of genetic instability (
  • E2F4 promoter occupancy is globally associated with TP53-repression targets, but not with TP53 activation targets, implicating E2F4 complexes as effectors of CDKN1A-dependent TP53-mediated repression
  • MAPPING cloned Y linked   status provisional
    Map cen - D16S2846 - D16S318 - E2F4 - D16S421 - D16S322 - qter
    Physical map
    FLJ35894 16q22.1 hypothetical protein FLJ35894 APPBP1 16q22 amyloid beta precursor protein binding protein 1, 59kDa CA7 16q22.1 carbonic anhydrase VII KIAA1348 CDH16 16q22.1 cadherin 16, KSP-cadherin RRAD 16q22 Ras-related associated with diabetes CGI-128 16q22.1-q22.3 CGI-128 protein CES2 16q22.1 carboxylesterase 2 (intestine, liver) FLJ21736 16q22.1 esterase 31 FLJ37464 16q22.1 hypothetical protein FLJ37464 CBFB 16q22.1 core-binding factor, beta subunit Lin10 16q22.1 lin-10 protein homolog MGC4655 16q22.1 hypothetical protein MGC4655 TRADD 16q22 TNFRSF1A-associated via death domain FBXL8 16q23.1 F-box and leucine-rich repeat protein 8 HSF4 16q21 heat shock transcription factor 4 NOL3 16qp21-q23 nucleolar protein 3 (apoptosis repressor with CARD domain) LOC283849 16q22.1 hypothetical protein LOC283849 E2F4 16q22.1 E2F transcription factor 4, p107/p130-binding ELMO3 16q23.1 engulfment and cell motility 3 (ced-12 homolog, C. elegans) FBXL9 16q23-q31 F-box and leucine-rich repeat protein 9 HSPC171 16q22.1 HSPC171 protein FHOD1 16q22 formin homology 2 domain containing 1 SLC9A5 16q22.1 solute carrier family 9 (sodium/hydrogen exchanger), isoform 5 DKFZP434I216 16q22.1 DKFZP434I216 protein FLJ40162 16q22.1 FLJ40162 protein FLJ11004 16q22.1 hypothetical protein FLJ11004 CGI-38 16q22.1 brain specific protein ZDHHC1 16q23.1 zinc finger, DHHC domain containing 1 HSD11B2 16q22 hydroxysteroid (11-beta) dehydrogenase 2 ATP6V0D1 16q22 ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d isoform 1 AGRP 16q22.1 agouti related protein homolog (mouse) FLJ13725 16q22.1 hypothetical protein FLJ13725 CTCF 16q22.1 CCCTC-binding factor (zinc finger protein)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2100 - 413 - 2007 17656449
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Endocrineparathyroid   highly
    Lymphoid/Immunelymph node   highly
    Nervousbrain   moderately
    Reproductivefemale systemuteruscervix highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a DNA binding domain,
  • a leucine zipper and a pRB binding domains
  • HOMOLOGY
    interspecies homolog to murine E2f4
    Homologene
    FAMILY
  • E2F/DP family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text cytoplasmic in quiescent differentiated cells but nuclear in proliferative cells
    basic FUNCTION
  • involved in cell proliferation
  • controlling genes regulating S phase entry and DNA synthesis
  • playing a critical role in the control of maturation cell in multiple cellular lineages (in mouse)
  • could exert a strong influence over the susceptibility to oncogenic transformation
  • acting to repress E2F-responsive genes, and having a strong capacity to inhibit transformation
  • may play an oncogenic rather than a tumor suppressor role in cells
  • in response to radiation, becomes active in the nucleus, enforces a stable G(2) arrest by target gene repression, and thus provides increased cell survival ability by minimizing propagation of cells that have irreparable DNA damage
  • induces cell death via multiple pathways in normal intestinal epithelial crypt cells but not in colon cancer cells (full mitogenic potential)
  • involved in gene repression and cell cycle exit, and also has poorly understood effects in differentiation
  • important in early stages of commitment to the lymphoid lineage
  • nuclear E2F4 may be determinant in the promotion of proliferation of human intestinal epithelial crypt cells and colorectal cancer cells
  • is required for cardiomyocyte proliferation, suggesting a function for E2F4 in mitosis
  • E2F4 and RB1 play independent cell-intrinsic roles in fetal erythropoiesis
  • involved in gene repression
  • is implicated in maintaining the G(0)/G(1) cell cycle state via transcriptional repression of genes that encode proteins required for S-phase progression
  • plays an important role in enabling osteoblast progenitors to exit the cell cycle and subsequently differentiate thereby contributing to the commitment of these cells to the bone lineage
  • can inhibit hypoxia-induced cell death in isolated ventricular cardiomyocytes
  • essential negative function of E2F4 in cardiac myocyte apoptosis
  • plays a critical role in cell cycle progression of normal and cancerous intestinal epithelial cells
  • believed to exhibit crucial control over the maintenance of a differentiated state of neurons
  • in contrast to E2F1 and E2F3, which sensitize to death, E2F4 plays a crucial protective role in neuronal death evoked by DNA damage, hypoxia, and global ischemic insult
  • likely plays a protective role in neurons from ischemic insult by forming repressive complexes that prevent prodeath factors such as Myb from being expressed
  • E2F4 and E2F5 display overlapping roles in controlling the normal development of the male reproductive system
  • CELLULAR PROCESS cell cycle
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • complex MADH3/E2F4/E2F5/DP1/RBL1
  • linking the TGFB receptor to CMYC repression
  • E2F4-RBL2 transcriptional repressor complex is a cell-cycle inhibitor in mitotic cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds directly to the proximal promoter of the Rb gene
  • cellular function of CDKN1B as a transcriptional regulator in association with RBL2/E2F4 complexes that could be relevant for tumorigenesis
  • TRIM28 has anti-proliferative activity in lung cancers via repression of E2F3, E2F4 that are critical for cell proliferation
  • cooperated with E2F4 to promote a state of deepened repression at cell cycle genes during differentiation
  • by coopting E2F4, E2F5 regulation of cell cycle genes, MCIDAS drives massive centriole assembly in epithelial progenitors in a manner required for multiciliate cell differentiation
  • gain of function mutant TP53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene expression
  • PHF8 by controlling E2F4 expression maintains endothelial function
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate cancer
    tumoral somatic mutation      
    in adult cell leukemia and childhood acute lymphoid leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    inhibiting transcription factors E2F4 and E2F5 having possible usefulness as targets in anti-cancer therapy
    cancerhemopathy 
    E2F4 is a target for developing novel and less toxic treatments for sporadic Burkitt lymphoma (sBL)
    ANIMAL & CELL MODELS