E2F4: A Key Regulator of Cell Cycle and Transcription
E2F Transcription Factor 4, p107/p130-Binding Partner
Gene Information Card
| Symbol | E2F4 |
|---|---|
| Full Name | E2F transcription factor 4, p107/p130-binding |
| Gene Type | Protein-coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 1874 ncbi.nlm.nih.gov/gene/1874 |
| Ensembl ID | ENSG00000105298 |
| UniProt ID | Q16254 |
| OMIM ID | 600967 |
| HGNC ID | 3118 |
| Aliases | E2F-4, p107/p130-binding protein |
Description
E2F4 is a member of the E2F family of transcription factors that play a crucial role in the regulation of cell cycle progression and DNA replication. Unlike other E2F family members, E2F4 primarily functions as a transcriptional repressor by binding to pocket proteins p107 and p130, and is involved in the G1/S phase transition. It is ubiquitously expressed and its activity is tightly regulated through phosphorylation and protein-protein interactions. Dysregulation of E2F4 has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Overexpression and altered subcellular localization of E2F4 contribute to uncontrolled cell proliferation | ClinVar, COSMIC |
| Breast Cancer | E2F4 mutations and amplification lead to disrupted cell cycle control | COSMIC, NCBI |
| Gastric Cancer | E2F4 frameshift mutations in microsatellite instability-high tumors | COSMIC, PubMed |
| Lung Cancer | E2F4 overexpression associated with poor prognosis | COSMIC, NCBI |
| Prostate Cancer | E2F4 dysregulation promotes androgen-independent growth | COSMIC |
| Bladder Cancer | E2F4 mutations found in transitional cell carcinoma | COSMIC |
| Hepatocellular Carcinoma | E2F4 upregulation linked to tumor progression | COSMIC |
| Endometrial Cancer | E2F4 frameshift mutations in microsatellite instability | COSMIC |
| Ovarian Cancer | E2F4 overexpression correlates with advanced stage | COSMIC |
| Pancreatic Cancer | E2F4 alterations in pancreatic ductal adenocarcinoma | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Adrenal gland | 15.2 | Medium |
| Brain | 18.7 | Medium |
| Breast | 14.3 | Medium |
| Colon | 22.1 | High |
| Esophagus | 16.8 | Medium |
| Heart | 11.4 | Medium |
| Kidney | 19.5 | Medium |
| Liver | 20.3 | High |
| Lung | 17.6 | Medium |
| Lymph node | 13.9 | Medium |
| Ovary | 15.7 | Medium |
| Pancreas | 14.2 | Medium |
| Prostate | 16.1 | Medium |
| Skin | 12.8 | Medium |
| Small intestine | 21.4 | High |
| Spleen | 18.9 | Medium |
| Stomach | 19.8 | Medium |
| Testis | 23.5 | High |
| Thyroid | 15.5 | Medium |
| Urinary bladder | 17.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 25.3 | Cervical adenocarcinoma |
| MCF7 | 22.7 | Breast cancer |
| A549 | 20.1 | Lung carcinoma |
| HCT116 | 28.4 | Colorectal carcinoma |
| HEK293 | 18.9 | Embryonic kidney |
| K562 | 16.5 | Leukemia |
| HepG2 | 21.8 | Hepatocellular carcinoma |
| PC3 | 19.2 | Prostate cancer |
| U2OS | 23.6 | Osteosarcoma |
| T47D | 24.1 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1096_1097insA | Frameshift | 0.5% in colorectal cancer | Loss of function; truncated protein |
| c.1102_1103delAG | Frameshift | 0.3% in gastric cancer | Loss of function; truncated protein |
| p.Ser121Leu | Missense | 0.1% in breast cancer | Altered DNA-binding affinity |
| p.Arg177His | Missense | 0.2% in lung cancer | Reduced transcriptional activity |
| p.Glu192Lys | Missense | 0.1% in prostate cancer | Impaired pocket protein binding |
| c.1150_1151insC | Frameshift | 0.4% in endometrial cancer | Loss of function |
| p.Thr214Ala | Missense | 0.05% in bladder cancer | Unknown significance |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., c.1096_1097insA, c.1102_1103delAG) result in truncated proteins lacking the transactivation domain, leading to loss of transcriptional repression activity.
Gain of Function (GOF)
Not well-documented; some missense mutations (e.g., p.Ser121Leu) may alter DNA-binding specificity, potentially enhancing oncogenic transcription.
Dominant Negative (DN)
Missense mutations affecting the pocket protein-binding domain (e.g., p.Glu192Lys) may interfere with wild-type E2F4 function by sequestering p107/p130.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell Cycle
• G1/S Transition (Reactome: R-HSA-69206)
• E2F-mediated regulation of DNA replication (Reactome: R-HSA-69236)
• p53-independent G1/S DNA damage checkpoint (Reactome: R-HSA-69615)
• Transcriptional regulation by E2F4 (KEGG: hsa04110)
• Cell cycle (KEGG: hsa04110)
Protein Summary
E2F4 is a 413-amino acid protein (UniProt Q16254) that contains a conserved DNA-binding domain, a dimerization domain, and a transactivation domain. It forms heterodimers with DP1 or DP2 and binds to E2F recognition sites in the promoters of target genes. E2F4 predominantly localizes to the nucleus in quiescent cells and is exported to the cytoplasm upon cell cycle entry. Its interaction with pocket proteins p107 and p130 mediates transcriptional repression of genes required for S-phase entry. Post-translational modifications include phosphorylation and acetylation, which modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| E2F4 Knockout HEK293 Cell Line | EDJ-KQ121 | Human | 1874 | Details Get a Quote |
| E2F4 Knockout A-549 Cell Line | EDJ-KQ18575 | Human | 1874 | Details Get a Quote |
| E2F4 Knockout HCT 116 Cell Line | EDJ-KQ18576 | Human | 1874 | Details Get a Quote |
| E2F4 Knockout HeLa Cell Line | EDJ-KQ18577 | Human | 1874 | Details Get a Quote |
