The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These ... See more...

Aliases for E2F4 Gene

Aliases for E2F4 Gene

  • E2F Transcription Factor 4 2 3 5
  • E2F-4 2 3 4
  • E2F Transcription Factor 4, P107/P130-Binding 2 3
  • Transcription Factor E2F4 3 4
  • P107/P130-Binding Protein 3
  • E2F4 5

External Ids for E2F4 Gene

Previous GeneCards Identifiers for E2F4 Gene

  • GC16P057920
  • GC16P067603
  • GC16P066962
  • GC16P067002
  • GC16P065783
  • GC16P067226
  • GC16P053100

Summaries for E2F4 Gene

Entrez Gene Summary for E2F4 Gene

  • The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein binds to all three of the tumor suppressor proteins pRB, p107 and p130, but with higher affinity to the last two. It plays an important role in the suppression of proliferation-associated genes, and its gene mutation and increased expression may be associated with human cancer. [provided by RefSeq, Jul 2008]

GeneCards Summary for E2F4 Gene

E2F4 (E2F Transcription Factor 4) is a Protein Coding gene. Diseases associated with E2F4 include Colorectal Cancer and Retinoblastoma. Among its related pathways are Transcriptional activity of SMAD2/SMAD3-SMAD4 heterotrimer and E2F transcription factor network. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is E2F5.

UniProtKB/Swiss-Prot Summary for E2F4 Gene

  • Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F4 binds with high affinity to RBL1 and RBL2. In some instances can also bind RB1. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis.

Gene Wiki entry for E2F4 Gene

Additional gene information for E2F4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for E2F4 Gene

Genomics for E2F4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for E2F4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around E2F4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for E2F4

Top Transcription factor binding sites by QIAGEN in the E2F4 gene promoter:
  • AP-1
  • MyoD
  • NRSF form 1
  • NRSF form 2
  • p53

Genomic Locations for E2F4 Gene

Genomic Locations for E2F4 Gene
chr16:67,192,155-67,198,918
(GRCh38/hg38)
Size:
6,764 bases
Orientation:
Plus strand
chr16:67,226,068-67,232,821
(GRCh37/hg19)
Size:
6,754 bases
Orientation:
Plus strand

Genomic View for E2F4 Gene

Genes around E2F4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
E2F4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for E2F4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for E2F4 Gene

Proteins for E2F4 Gene

  • Protein details for E2F4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q16254-E2F4_HUMAN
    Recommended name:
    Transcription factor E2F4
    Protein Accession:
    Q16254
    Secondary Accessions:
    • A6NGR8
    • B5BU56
    • Q12991
    • Q15328

    Protein attributes for E2F4 Gene

    Size:
    413 amino acids
    Molecular mass:
    43960 Da
    Quaternary structure:
    • Component of the DRTF1/E2F transcription factor complex. Binds cooperatively with TFDP1/Dp-1 to E2F sites. The E2F4/TFDP1 dimer interacts preferentially with pocket protein RBL1, which inhibits the E2F transactivation domain. Lower affinity interaction has been found with retinoblastoma protein RB1. Interacts with TRRAP, which probably mediates its interaction with histone acetyltransferase complexes, leading to transcription activation. Interacts with HCFC1. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5). Interacts with CEBPA (when phosphorylated) (PubMed:15107404).

    Three dimensional structures from OCA and Proteopedia for E2F4 Gene

neXtProt entry for E2F4 Gene

Post-translational modifications for E2F4 Gene

Other Protein References for E2F4 Gene

No data available for DME Specific Peptides for E2F4 Gene

Domains & Families for E2F4 Gene

Gene Families for E2F4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for E2F4 Gene

InterPro:
Blocks:
  • Transcription factor E2F/dimerisation partner (TDP)
ProtoNet:

Suggested Antigen Peptide Sequences for E2F4 Gene

GenScript: Design optimal peptide antigens:
  • Transcription factor E2F4 (E2F4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q16254

UniProtKB/Swiss-Prot:

E2F4_HUMAN :
  • Belongs to the E2F/DP family.
Family:
  • Belongs to the E2F/DP family.
genes like me logo Genes that share domains with E2F4: view

Function for E2F4 Gene

Molecular function for E2F4 Gene

UniProtKB/Swiss-Prot Function:
Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F4 binds with high affinity to RBL1 and RBL2. In some instances can also bind RB1. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis.
GENATLAS Biochemistry:
transcription factor E2F4,involved in cell proliferation,controlling genes regulating S phase entry and DNA synthesis

Phenotypes From GWAS Catalog for E2F4 Gene

Gene Ontology (GO) - Molecular Function for E2F4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IEA,IDA 10488129
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISM 19274049
GO:0001216 bacterial-type RNA polymerase transcriptional activator activity, sequence-specific DNA binding IDA 17062573
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 11418595
GO:0003677 DNA binding IEA,IMP 11418595
genes like me logo Genes that share ontologies with E2F4: view
genes like me logo Genes that share phenotypes with E2F4: view

Animal Models for E2F4 Gene

MGI Knock Outs for E2F4:

Animal Model Products

CRISPR Products

Transcription Factor Targets for E2F4 Gene

Selected GeneGlobe predicted Target genes for E2F4
Targeted motifs for E2F4 Gene
HOMER Transcription Factor Regulatory Elements motif E2F4
  • Consensus sequence: GGCGGGAAAH Submotif: canonical Cell Type: K562 GEO ID: GSE31477

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for E2F4

No data available for Enzyme Numbers (IUBMB) and Human Phenotype Ontology for E2F4 Gene

Localization for E2F4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for E2F4 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for E2F4 gene
Compartment Confidence
nucleus 5
cytosol 3
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for E2F4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IEA,ISA --
GO:0005623 cell IEA --
GO:0005634 nucleus IEA,IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IEA --
genes like me logo Genes that share ontologies with E2F4: view

Pathways & Interactions for E2F4 Gene

PathCards logo

SuperPathways for E2F4 Gene

SuperPathway Contained pathways
1 Cyclins and Cell Cycle Regulation
.67
.67
.36
.31
2 Cell cycle Cell cycle (generic schema)
.38
.38
3 Transcriptional activity of SMAD2/SMAD3-SMAD4 heterotrimer
4 Cell cycle
5 MAPK Signaling: Mitogens
genes like me logo Genes that share pathways with E2F4: view

Pathways by source for E2F4 Gene

4 GeneGo (Thomson Reuters) pathways for E2F4 Gene
  • Cell cycle Cell cycle (generic schema)
  • Cell cycle ESR1 regulation of G1/S transition
  • Cell cycle Regulation of G1/S transition (part 2)
  • Cell cycle Transition and termination of DNA replication
2 R&D Systems pathways for E2F4 Gene
16 Qiagen pathways for E2F4 Gene
  • BRCA1 Pathway
  • Breast Cancer Regulation by Stathmin1
  • Cell Cycle Control by BTG Proteins
  • Chks in Checkpoint Regulation
  • Colorectal Cancer Metastasis

SIGNOR curated interactions for E2F4 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for E2F4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle IEA --
GO:0000122 negative regulation of transcription by RNA polymerase II IBA 21873635
GO:0000278 mitotic cell cycle IEA --
GO:0002064 epithelial cell development IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
genes like me logo Genes that share ontologies with E2F4: view

Drugs & Compounds for E2F4 Gene

(5) Drugs for E2F4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for E2F4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with E2F4: view

Transcripts for E2F4 Gene

mRNA/cDNA for E2F4 Gene

1 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for E2F4

Alternative Splicing Database (ASD) splice patterns (SP) for E2F4 Gene

No ASD Table

Relevant External Links for E2F4 Gene

GeneLoc Exon Structure for
E2F4

Expression for E2F4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for E2F4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for E2F4 Gene

This gene is overexpressed in Fetal Liver (14.1), Pancreas (13.0), Peripheral blood mononuclear cells (8.5), and Colon (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for E2F4 Gene



Protein tissue co-expression partners for E2F4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for E2F4

SOURCE GeneReport for Unigene cluster for E2F4 Gene:

Hs.108371

mRNA Expression by UniProt/SwissProt for E2F4 Gene:

Q16254-E2F4_HUMAN
Tissue specificity: Found in all tissue examined including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Evidence on tissue expression from TISSUES for E2F4 Gene

  • Liver(4.5)
  • Kidney(4.5)
  • Nervous system(3.6)
  • Intestine(3)
  • Skin(3)
  • Bone marrow(2.8)
  • Lung(2.8)
  • Muscle(2.8)
  • Lymph node(2.7)
  • Blood(2.6)
  • Heart(2.6)
  • Spleen(2.5)
  • Thyroid gland(2.5)
  • Stomach(2.4)
  • Pancreas(2.4)
  • Adrenal gland(2.1)
genes like me logo Genes that share expression patterns with E2F4: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for E2F4 Gene

Orthologs for E2F4 Gene

This gene was present in the common ancestor of animals.

Orthologs for E2F4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia E2F4 30 31
  • 97.79 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia E2F4 30 31
  • 90.16 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia E2F4 30 31
  • 89.5 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia E2f4 30
  • 89.38 (n)
Mouse
(Mus musculus)
Mammalia E2f4 30 17 31
  • 88.1 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia E2F4 31
  • 81 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia E2F4 31
  • 72 (a)
OneToOne
Chicken
(Gallus gallus)
Aves E2F4 30 31
  • 73.23 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia E2F4 31
  • 74 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia e2f4 30
  • 68.14 (n)
Str.4585 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.24786 30
Zebrafish
(Danio rerio)
Actinopterygii e2f4 30 31
  • 65.4 (n)
OneToOne
wufb72f07 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.6688 30
Fruit Fly
(Drosophila melanogaster)
Insecta E2f2 31
  • 26 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea efl-1 31 32
  • 30 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.1239 31
  • 65 (a)
OneToOne
Species where no ortholog for E2F4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for E2F4 Gene

ENSEMBL:
Gene Tree for E2F4 (if available)
TreeFam:
Gene Tree for E2F4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for E2F4: view image

Paralogs for E2F4 Gene

Paralogs for E2F4 Gene

(3) SIMAP similar genes for E2F4 Gene using alignment to 5 proteins:

  • E2F4_HUMAN
  • H3BMP3_HUMAN
  • H3BTM3_HUMAN
  • H3BVE4_HUMAN
  • I3L1B6_HUMAN

Pseudogenes.org Pseudogenes for E2F4 Gene

genes like me logo Genes that share paralogs with E2F4: view

Variants for E2F4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for E2F4 Gene

E2F4_HUMAN-Q16254
The poly-Ser region of E2F4 is polymorphic and the number of Ser varies in the population (from 8 to 17). The variation might be associated with tumorigenesis.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for E2F4 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
rs1801013 - p.Thr293Pro

Additional dbSNP identifiers (rs#s) for E2F4 Gene

Structural Variations from Database of Genomic Variants (DGV) for E2F4 Gene

Variant ID Type Subtype PubMed ID
nsv1160429 CNV deletion 26073780
nsv457513 CNV loss 19166990
nsv471092 CNV gain 18288195
nsv522852 CNV gain 19592680
nsv524363 CNV loss 19592680
nsv524492 CNV loss 19592680
nsv572905 CNV loss 21841781
nsv827707 CNV loss 20364138
nsv952044 CNV deletion 24416366

Variation tolerance for E2F4 Gene

Residual Variation Intolerance Score: 36.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.97; 19.98% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for E2F4 Gene

Human Gene Mutation Database (HGMD)
E2F4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
E2F4

SNP Genotyping and Copy Number Assay Products

Disorders for E2F4 Gene

MalaCards: The human disease database

(11) MalaCards diseases for E2F4 Gene - From: LncRNADisease, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
colorectal cancer
  • crc
retinoblastoma
  • rb1
epilepsy, idiopathic generalized 3
  • epilepsy, idiopathic generalized, susceptibility to, 3
glioblastoma multiforme
  • adult glioblastoma multiforme
retinal cancer
  • malignant neoplasm of retina
- elite association - COSMIC cancer census association via MalaCards
Search E2F4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for E2F4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with E2F4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for E2F4 Gene

Publications for E2F4 Gene

  1. E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. (PMID: 7892279) Sardet C … Weinberg RA (Proceedings of the National Academy of Sciences of the United States of America 1995) 2 3 4 23
  2. E2F-4, a new member of the E2F transcription factor family, interacts with p107. (PMID: 7958924) Ginsberg D … Livingston DM (Genes & development 1994) 2 3 4 23
  3. E2F transcriptional activation requires TRRAP and GCN5 cofactors. (PMID: 11418595) Lang SE … Hearing P (The Journal of biological chemistry 2001) 3 4 23
  4. Genomic structure and mutation screening of the E2F4 gene in human tumors. (PMID: 10797289) Schwemmle S … Pfeifer GP (International journal of cancer 2000) 3 4 23
  5. Various AGC repeat numbers in the coding region of the human transcription factor gene E2F-4. (PMID: 10679953) Zhong X … Shimatake H (Human mutation 2000) 3 4 23

Products for E2F4 Gene

Sources for E2F4 Gene