Details for: E4F1

Gene ID: 1877

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: E4F1

Ensembl ID: ENSG00000167967

Description: E4F transcription factor 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Camp response element binding
    (GO:0035497)
  • Cell division
    (GO:0051301)
  • Cytoplasm
    (GO:0005737)
  • Dna-binding transcription activator activity, rna polymerase ii-specific
    (GO:0001228)
  • Dna-binding transcription factor activity
    (GO:0003700)
  • Dna-binding transcription repressor activity, rna polymerase ii-specific
    (GO:0001227)
  • Dna replication
    (GO:0006260)
  • Metal ion binding
    (GO:0046872)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Nuclear body
    (GO:0016604)
  • Nucleoplasm
    (GO:0005654)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Protein binding
    (GO:0005515)
  • Protein ubiquitination
    (GO:0016567)
  • Regulation of cell cycle
    (GO:0051726)
  • Regulation of cell cycle process
    (GO:0010564)
  • Regulation of mitotic cell cycle, embryonic
    (GO:0009794)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii-specific dna-binding transcription factor binding
    (GO:0061629)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Rna polymerase ii transcription regulatory region sequence-specific dna binding
    (GO:0000977)
  • Spindle
    (GO:0005819)
  • Transferase activity
    (GO:0016740)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • early lymphoid progenitor CL0000936
    CSI 3.15
    rCSI 2.77%
    PRS 88.87
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.96
    rCSI 2.28%
    PRS 87.8
  • lung neuroendocrine cell CL1000223
    CSI 2.88
    rCSI 4.26%
    PRS 87.4
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.77
    rCSI 1.94%
    PRS 87.92
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.56
    rCSI 2.61%
    PRS 92.1
  • precursor B cell CL0000817
    CSI 2.49
    rCSI 2.18%
    PRS 90.32
  • goblet cell CL0000160
    CSI 2.42
    rCSI 2.28%
    PRS 82.68
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.39
    rCSI 2.97%
    PRS 66.05
  • myeloid leukocyte CL0000766
    CSI 2.38
    rCSI 2.2%
    PRS 85.89
  • lung ciliated cell CL1000271
    CSI 2.37
    rCSI 2.75%
    PRS 77.69
  • ionocyte CL0005006
    CSI 2.24
    rCSI 2.4%
    PRS 86.33
  • ciliated epithelial cell CL0000067
    CSI 2.21
    rCSI 1.94%
    PRS 74.58
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.21
    rCSI 1.91%
    PRS 87.88
  • ependymal cell CL0000065
    CSI 2.13
    rCSI 4.33%
    PRS 64.47
  • intestine goblet cell CL0019031
    CSI 2.13
    rCSI 1.89%
    PRS 82.24
  • colonocyte CL1000347
    CSI 2.08
    rCSI 2.97%
    PRS 84.22
  • stem cell CL0000034
    CSI 1.94
    rCSI 1.87%
    PRS 79.13
  • colon epithelial cell CL0011108
    CSI 1.92
    rCSI 2.01%
    PRS 82.02
  • transit amplifying cell of colon CL0009011
    CSI 1.85
    rCSI 2.17%
    PRS 85.95
  • BEST4+ enteroycte CL4030026
    CSI 1.81
    rCSI 2.25%
    PRS 85.05
  • erythrocyte CL0000232
    CSI 1.67
    rCSI 3.78%
    PRS 84.17
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.44
    rCSI 2.54%
    PRS 67.68
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.44
    rCSI 2.86%
    PRS 93.65
  • peripheral nervous system neuron CL2000032
    CSI 1.31
    rCSI 1.78%
    PRS 76.89
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.3
    rCSI 2.9%
    PRS 68.99
  • mesenchymal cell CL0008019
    CSI 0.95
    rCSI 2.41%
    PRS 78.27
  • retinal cone cell CL0000573
    CSI 0.94
    rCSI 1.51%
    PRS 75.47
  • dopaminergic neuron CL0000700
    CSI 0.76
    rCSI 4.29%
    PRS 71.45

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [E4F1](/details-gene/1877) is a protein-coding gene located on chromosome 16p13.3 that encodes the E4F transcription factor 1. This protein functions as a versatile regulator of gene expression, possessing both activator and repressor activities that are crucial for fundamental cellular processes. Its primary annotated functions include the regulation of the cell cycle, DNA replication, and transcription by RNA polymerase II. **Overall**, expression data indicates that [E4F1](/details-gene/1877) is highly significant in various progenitor populations, particularly in the hematopoietic lineage such as [early lymphoid progenitor](/details-cell/CL0000936) cells, as well as in specific differentiated cell types including monocytes and specialized epithelial cells. Its well-documented interactions with key cell cycle regulators like p53 and pRB highlight its role as a gatekeeper of cellular proliferation [Link](https://pubmed.ncbi.nlm.nih.gov/10644996/) [Link](https://pubmed.ncbi.nlm.nih.gov/10869426/). ## Cellular Roles and Expression Landscape The expression profile of [E4F1](/details-gene/1877) suggests a widespread but important role across multiple, distinct cellular contexts. **Overall**, the gene shows the highest significance in progenitor cells and actively cycling populations within the immune system. It is a top marker in [early lymphoid progenitor](/details-cell/CL0000936) (CSI: 3.15), [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 2.21), and [precursor B cell](/details-cell/CL0000817) (CSI: 2.49), which is consistent with its established role in regulating cell division and DNA replication. Beyond progenitor cells, [E4F1](/details-gene/1877) is also highly significant in several mature myeloid and lymphoid lineages. These include [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 2.96), [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 2.77), and [myeloid leukocyte](/details-cell/CL0000766) (CSI: 2.38). This pattern suggests an ongoing transcriptional regulatory function in these differentiated immune cells. Interestingly, [E4F1](/details-gene/1877) also demonstrates high significance in a diverse array of specialized, non-immune cell types, such as [lung neuroendocrine cell](/details-cell/CL1000223) (CSI: 2.88), [goblet cell](/details-cell/CL0000160) (CSI: 2.42), and [lung ciliated cell](/details-cell/CL1000271) (CSI: 2.37), indicating it may be involved in maintaining the unique transcriptional programs of these terminally differentiated cells. ## Pathways and Molecular Function Functionally, [E4F1](/details-gene/1877) is a multifaceted transcription factor with roles in both promoting and inhibiting gene expression. Its molecular functions are dominated by DNA-binding activities, including [DNA-binding transcription activator activity, rna polymerase ii-specific](/details-cell/GO:0001228) and [DNA-binding transcription repressor activity, rna polymerase ii-specific](/details-cell/GO:0001227). This duality allows it to finely tune transcriptional programs that govern key biological processes. The most prominent annotated processes are related to cell proliferation, including [Cell division](/details-cell/GO:0051301), [Dna replication](/details-cell/GO:0006260), and [Regulation of cell cycle](/details-cell/GO:0051726). This is supported by multiple studies showing that [E4F1](/details-gene/1877) can inhibit cell growth, partly through the stabilization of the CDK inhibitor p21 [Link](https://doi.org/10.1128/mcb.18.1.459), and that its growth-arrest function involves p53 [Link](https://doi.org/10.1038/sj.onc.1203250). Furthermore, it is implicated in [Protein ubiquitination](/details-cell/GO:0016567), suggesting it may also regulate protein stability. The gene product is localized to both the [Cytoplasm](/details-cell/GO:0005737) and the [Nucleoplasm](/details-cell/GO:0005654), consistent with its function as a transcription factor that may shuttle between compartments. ## Research Directions The broad yet significant expression of [E4F1](/details-gene/1877) in both highly proliferative progenitor cells and terminally differentiated cells raises key questions about its context-dependent functions. **Proposed Hypotheses:** 1. Given its high significance in hematopoietic progenitors ([early lymphoid progenitor](/details-cell/CL0000936), [granulocyte monocyte progenitor cell](/details-cell/CL0000557)) and its fundamental role in cell cycle control, [E4F1](/details-gene/1877) may act as a critical checkpoint regulator during hematopoiesis, balancing the decision between self-renewal and lineage-specific differentiation. Its dysregulation could contribute to developmental blocks or uncontrolled proliferation characteristic of leukemia. 2. The high significance of [E4F1](/details-gene/1877) in diverse, post-mitotic cells such as [lung ciliated cell](/details-cell/CL1000271) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) suggests it plays a vital role in maintaining cellular identity and function. It may be required to actively repress cell cycle re-entry and sustain the expression of genes essential for specialized cellular tasks. **Experimental Approach:** To test the first hypothesis regarding its role in hematopoiesis, a conditional knockout of [E4F1](/details-gene/1877) could be generated in hematopoietic stem and progenitor cells (HSPCs) using a Cre-Lox system (e.g., Vav-iCre;E4F1-fl/fl mice). The consequence of its deletion could be assessed through competitive bone marrow transplantation assays to evaluate HSPC fitness *in vivo*. Furthermore, *in vitro* differentiation assays coupled with single-cell RNA-sequencing would allow for a high-resolution mapping of the cell fate trajectories and transcriptional states of [E4F1](/details-gene/1877)-deficient cells, revealing specific differentiation blocks or lineage biases. **Therapeutic Potential:** As a transcription factor deeply involved in cell cycle regulation and with documented tumor-suppressive activities [Link](https://doi.org/10.1128/mcb.19.7.4739), [E4F1](/details-gene/1877) presents an interesting, albeit challenging, therapeutic target. Its ability to induce growth arrest suggests that strategies aimed at **activating** its function or restoring its expression in cancer cells where it is silenced could have anti-neoplastic effects. However, its nature as a transcription factor makes it difficult to target directly with small molecules. Moreover, its widespread expression pattern raises concerns about potential on-target toxicities in healthy, proliferating tissues. Future research into the specific upstream pathways that regulate [E4F1](/details-gene/1877) activity in cancer cells may reveal more druggable nodes for therapeutic intervention.

Genular Protein ID: 3085525268

Symbol: E4F1_HUMAN

Name: Transcription factor E4F1

UniProtKB Accession Codes:

Q66K89 A8K2R4 O00146

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 5 Ensembl 1 ExpressionAtlas 1 GO 22 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 3 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9121437

Title: The adenovirus E1A-regulated transcription factor E4F is generated from the human homolog of nuclear factor phiAP3.

PubMed ID: 9121437

DOI: 10.1128/mcb.17.4.1890

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9530632

Title: Chromosomal location and tissue expression of the gene encoding the adenovirus E1A-regulated transcription factor E4F in humans and mice.

PubMed ID: 9530632

DOI: 10.1007/s003359900758

PubMed ID: 9418893

Title: Adenovirus E1A-regulated transcription factor p120E4F inhibits cell growth and induces the stabilization of the cdk inhibitor p21WAF1.

PubMed ID: 9418893

DOI: 10.1128/mcb.18.1.459

PubMed ID: 9512539

Title: Mutational analysis of p50E4F suggests that DNA binding activity is mediated through an alternative structure in a zinc finger domain that is regulated by phosphorylation.

PubMed ID: 9512539

DOI: 10.1093/nar/26.7.1681

PubMed ID: 10373523

Title: Suppression of E1A-mediated transformation by the p50E4F transcription factor.

PubMed ID: 10373523

DOI: 10.1128/mcb.19.7.4739

PubMed ID: 10644996

Title: p53 is involved in the p120E4F-mediated growth arrest.

PubMed ID: 10644996

DOI: 10.1038/sj.onc.1203250

PubMed ID: 10869426

Title: pRB binds to and modulates the transrepressing activity of the E1A-regulated transcription factor p120E4F.

PubMed ID: 10869426

DOI: 10.1073/pnas.130198397

PubMed ID: 11283272

Title: Cyclin A is a mediator of p120E4F-dependent cell cycle arrest in G1.

PubMed ID: 11283272

DOI: 10.1128/mcb.21.8.2956-2966.2001

PubMed ID: 12446718

Title: Association of p14ARF with the p120E4F transcriptional repressor enhances cell cycle inhibition.

PubMed ID: 12446718

DOI: 10.1074/jbc.m210978200

PubMed ID: 14645522

Title: Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2.

PubMed ID: 14645522

DOI: 10.1128/mcb.23.24.9104-9116.2003

PubMed ID: 12730668

Title: Modulation of p120E4F transcriptional activity by the Gam1 adenoviral early protein.

PubMed ID: 12730668

DOI: 10.1038/sj.onc.1206379

PubMed ID: 15579445

Title: E4F1, a novel estrogen-responsive gene in possible atheroprotection, revealed by microarray analysis.

PubMed ID: 15579445

DOI: 10.1016/s0002-9440(10)63253-1

PubMed ID: 14729613

Title: Identification of the E1A-regulated transcription factor p120 E4F as an interacting partner of the RASSF1A candidate tumor suppressor gene.

PubMed ID: 14729613

DOI: 10.1158/0008-5472.can-03-2622

PubMed ID: 15805267

Title: Transcriptional regulation of cyclin A2 by RASSF1A through the enhanced binding of p120E4F to the cyclin A2 promoter.

PubMed ID: 15805267

DOI: 10.1158/0008-5472.can-04-3593

PubMed ID: 15876874

Title: p14ARF interacts with the SUMO-conjugating enzyme Ubc9 and promotes the sumoylation of its binding partners.

PubMed ID: 15876874

DOI: 10.4161/cc.4.4.1597

PubMed ID: 17110336

Title: E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation.

PubMed ID: 17110336

DOI: 10.1016/j.cell.2006.09.031

PubMed ID: 16882984

Title: E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells.

PubMed ID: 16882984

DOI: 10.1101/gad.1453406

PubMed ID: 16652157

Title: The LIM-only protein FHL2 is a negative regulator of E4F1.

PubMed ID: 16652157

DOI: 10.1038/sj.onc.1209567

PubMed ID: 16112766

Title: Interaction of the hepatitis B virus protein HBx with the human transcription regulatory protein p120E4F in vitro.

PubMed ID: 16112766

DOI: 10.1016/j.virusres.2005.07.003

PubMed ID: 17557114

Title: The role of LANP and ataxin 1 in E4F-mediated transcriptional repression.

PubMed ID: 17557114

DOI: 10.1038/sj.embor.7400983

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

Sequence Information:

  • Length: 784
  • Mass: 83496
  • Checksum: 60F6E711F2748FD8
  • Sequence:
    • MEGAMAVRVT AAHTAEAQAE AGREAGEGAV AAVAAALAPS GFLGLPAPFS EEDEDDVHRC 
GRCQAEFTAL EDFVQHKIQK ACQRAPPEAL PATPATTALL GQEVVPAAPG PEEPITVAHI 
VVEAASLAAD ISHASDLVGG GHIKEVIVAA EAELGDGEMA EAPGSPRQQG LGLAGEGEQA 
QVKLLVNKDG RYVCALCHKT FKTGSILKAH MVTHSSRKDH ECKLCGASFR TKGSLIRHHR 
RHTDERPYKC SKCGKSFRES GALTRHLKSL TPCTEKIRFS VSKDVVVSKE DARAGSGAGA 
AGLGTATSSV TGEPIETSPV IHLVTDAKGT VIHEVHVQMQ ELSLGMKALA PEPPVSQELP 
CSSEGSRENL LHQAMQNSGI VLERAAGEEG ALEPAPAAGS SPQPLAVAAP QLPVLEVQPL 
ETQVASEASA VPRTHPCPQC SETFPTAATL EAHKRGHTGP RPFACAQCGK AFPKAYLLKK 
HQEVHVRERR FRCGDCGKLY KTIAHVRGHR RVHSDERPYP CPKCGKRYKT KNAQQVHFRT 
HLEEKPHVCQ FCSRGFREKG SLVRHVRHHT GEKPFKCYKC GRGFAEHGTL NRHLRTKGGC 
LLEVEELLVS EDSPAAATTV LTEDPHTVLV EFSSVVADTQ EYIIEATADD AETSEATEII 
EGTQTEVDSH IMKVVQQIVH QASAGHQIIV QNVTMDEETA LGPEAAAADT ITIATPESLT 
EQVAMTLASA ISEGTVLAAR AGTSGTEQAT VTMVSSEDIE ILEHAGELVI ASPEGQLEVQ 
TVIV