Description: Homo sapiens E2F transcription factor 4, p107/p130-binding (E2F4), mRNA. RefSeq Summary (NM_001950): 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]. Transcript (Including UTRs) Position: hg19 chr16:67,226,068-67,232,821 Size: 6,754 Total Exon Count: 10 Strand: + Coding Region Position: hg19 chr16:67,226,131-67,232,026 Size: 5,896 Coding Exon Count: 10
ID:E2F4_HUMAN DESCRIPTION: RecName: Full=Transcription factor E2F4; Short=E2F-4; 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. SUBUNIT: 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. SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Found in all tissue examined including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. DEVELOPMENTAL STAGE: Present in the growth-arrested state, its abundance does not change significantly as cells move into and through the cell cycle. PTM: Differentially phosphorylated in vivo. POLYMORPHISM: 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. SIMILARITY: Belongs to the E2F/DP family. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/e2f4/";
To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): E2F4 CDC HuGE Published Literature: E2F4 Positive Disease Associations: Coronary Disease
, Lipoproteins, HDL Related Studies:
Coronary Disease Guillaume Lettre et al. PLoS genetics 2011, Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project., PLoS genetics.
[PubMed 21347282]
suggest that no major loci uniquely explain the high prevalence of CHD in African Americans.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q16254
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
U15641 - Human transcription factor E2F-4 mRNA, complete cds. S75174 - E2F-4=transcription factor [human, Nalm6 and HeLa cells, mRNA, 1539 nt]. BC010079 - Homo sapiens cDNA clone IMAGE:4329093, **** WARNING: chimeric clone ****. BC031071 - Homo sapiens E2F transcription factor 4, p107/p130-binding, mRNA (cDNA clone IMAGE:5288781), with apparent retained intron. BC021050 - Homo sapiens E2F transcription factor 4, p107/p130-binding, mRNA (cDNA clone IMAGE:3504728). BC033180 - Homo sapiens E2F transcription factor 4, p107/p130-binding, mRNA (cDNA clone MGC:45817 IMAGE:4585569), complete cds. X86096 - Homo sapiens mRNA for transcription factor (E2F-4 gene). AB451425 - Homo sapiens E2F4 mRNA for E2F transcription factor 4, partial cds, clone: FLJ08135AAAF. DQ892803 - Synthetic construct clone IMAGE:100005433; FLH189887.01X; RZPDo839C0375D E2F transcription factor 4, p107/p130-binding (E2F4) gene, encodes complete protein. AB451292 - Homo sapiens E2F4 mRNA for E2F transcription factor 4, complete cds, clone: FLJ08135AAAN. JD021265 - Sequence 2289 from Patent EP1572962. JD030486 - Sequence 11510 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04110 - Cell cycle hsa04350 - TGF-beta signaling pathway
BioCarta from NCI Cancer Genome Anatomy Project h_etsPathway - METS affect on Macrophage Differentiation
Reactome (by CSHL, EBI, and GO)
Protein Q16254 (Reactome details) participates in the following event(s):
R-HSA-1226095 Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex R-HSA-1227671 Recruitment of HDAC1 by p107 (RBL1) R-HSA-1363311 p107 (RBL1) in complex with E2F4:DP1/2 binds to cyclin E/A:CDK2 R-HSA-6798282 TP53 and E2F4 bind the CDC25C gene R-HSA-1226094 Cyclin D:Cdk4/6 mediated phosphorylation of p130 (RBL2) and dissociation of phosphorylated p130 (RBL2) from DP1:E2F4/5 complex R-HSA-1227670 Recruitment of HDAC1 by p130 (RBL2) R-HSA-1362261 p130 (RBL2) associates with MuvB to form DREAM complex R-HSA-1363303 p130 (RBL2) in complex with E2F4/5:DP1/2 binds to cyclin E/A:CDK2 R-HSA-2127257 SMAD2/3:SMAD4 heterotrimer forms a complex with RBL1, E2F4/5 and DP1/2 R-HSA-8964550 The complex of HDAC1, RBL1 and E2F4 or HDAC1, RBL2, E2F4 or E2F5 binds E2F1 gene promoter R-HSA-8964561 The complex of HDAC1, RBL1 and E2F4 or HDAC1, RBL2, E2F4 or E2F5 binds MYBL2 gene promoter R-HSA-8964567 The complex of HDAC1, RBL1 and E2F4 or HDAC1, RBL2, E2F4 or E2F5 binds CDK1 gene promoter R-HSA-8964580 The complex of HDAC1, RBL1 and E2F4 or HDAC1, RBL2, E2F4 or E2F5 binds CCNA2 gene promoter R-HSA-8964465 DREAM complex binds the PCNA gene promoter R-HSA-8964471 DREAM complex binds the CDC25A gene promoter R-HSA-8964475 DREAM complex binds the TOP2A gene promoter R-HSA-8964482 DREAM complex binds the E2F1 gene promoter R-HSA-8964492 DREAM complex binds the RBL1 gene promoter R-HSA-8964498 DREAM complex binds the CDC6 gene promoter R-HSA-69231 Cyclin D associated events in G1 R-HSA-1538133 G0 and Early G1 R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest R-HSA-69236 G1 Phase R-HSA-453279 Mitotic G1-G1/S phases R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription R-HSA-1362300 Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 R-HSA-69278 Cell Cycle (Mitotic) R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer R-HSA-1640170 Cell Cycle R-HSA-212436 Generic Transcription Pathway R-HSA-170834 Signaling by TGF-beta Receptor Complex R-HSA-73857 RNA Polymerase II Transcription R-HSA-9006936 Signaling by TGF-beta family members R-HSA-74160 Gene expression (Transcription) R-HSA-162582 Signal Transduction
US Server
