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FLASH GENE
Symbol E2F6 contributors: mct/npt - updated : 17-05-2023
HGNC name E2F transcription factor 6
HGNC id 3120
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer heteromer , dimer
HOMOLOGY
Homologene
FAMILY
  • E2F/DP transcription factors family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • functioning as a repressor of E2F-dependent transcription during S phase
  • dominant-negative transcriptional repressor against other members of the E2F family (Kikuchi 2007)
  • provides a failsafe mechanism against loss of hematopoietic progenitor cells during proliferation (Kikuchi 2007)
  • playing a role in control of hypoxia-induced apoptosis through regulation of E2F1 (Yang 2008)
  • E2F6 serves to modulate E2F activity and protect cells including cardiomyocytes from apoptosis and improve survival
  • functions as a competing endogenous RNA, and transcriptional repressor, to promote ovarian cancer stemness
  • E2F-dependent transcription, through E2F6, determines the replication capacity of a cell, defined as the maximal amount of DNA a cell can synthesise per unit time during S-phase
  • E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells
  • E2F6, a pocket protein-independent transcription repressor, is essential for hepatocellular carcinoma (HCC) cell growth, and its activities are controlled by USP22-mediated deubiquitination
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with EPC1 (E2F6-EPC1 complex) (E2F6-EPC1 interacts with EZH2 and may regulate genes required for cell cycle progression) (Attwooll 2005)
  • INTERACTION
    DNA
    RNA
    small molecule other,
  • E2F6 binds preferentially to CpG islands in embryonic cells
  • protein
  • functions as an RB-independent repressor of gene transcription
  • SMARCA4, is an E2F6 interacting protein, and E2F6 may recruit SMARCA4 in transcriptional regulation of genes important for G1/S phase transition of the cell cycle
  • after replication stress, the checkpoint kinase CHEK1 phosphorylates E2F6, leading to its dissociation from promoters, and this promotes E2F-dependent transcription, which mediates cell survival by preventing DNA damage and cell death
  • E2F6 is strongly downregulated by NR2E1, and its expression inhibits beta cell proliferation
  • USP22 interacts with and stabilizes E2F6, resulting in the transcriptional repression of phosphatase DUSP1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    abrogated hypoxia-induced apoptosis and alteration of E2F1 (Yang 2008)
    constitutional       loss of function
    deregulated E2F6 levels evoked abnormal gene expression at transcriptional and post-transcriptional levels, leading to cardiac remodeling and dilated cardiomyopathy
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • independent risk factor for the prognosis of female Head and neck squamous cell carcinoma (HNSCC) patients
  • Therapy target
    ANIMAL & CELL MODELS