E2F1

gene
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Also known as RBP3

Summary

E2F1 (E2F transcription factor 1, HGNC:3113) is a protein-coding gene on chromosome 20q11.22, encoding Transcription factor E2F1 (Q01094). 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. It is a selective cancer dependency (DepMap: 15.8% of cell lines).

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 and another 2 members, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis.

Source: NCBI Gene 1869 — RefSeq curated summary.

At a glance

  • GWAS associations: 3
  • Clinical variants (ClinVar): 57 total
  • Druggable target: yes
  • Cancer dependency (DepMap): dependent in 15.8% of screened cell lines
  • Transcription factor: yes — 493 downstream targets (CollecTRI)
  • MANE Select transcript: NM_005225

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:3113
Approved symbolE2F1
NameE2F transcription factor 1
Location20q11.22
Locus typegene with protein product
StatusApproved
AliasesRBP3
Ensembl geneENSG00000101412
Ensembl biotypeprotein_coding
OMIM189971
Entrez1869

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000343380, ENST00000888354, ENST00000932103, ENST00000932104

RefSeq mRNA: 1 — MANE Select: NM_005225 NM_005225

CCDS: CCDS13224

Canonical transcript exons

ENST00000343380 — 7 exons

ExonStartEnd
ENSE000006613423367710533677330
ENSE000006613453367975533679974
ENSE000006613463368032633680416
ENSE000008600583367742633677540
ENSE000013864023367547733676979
ENSE000013875943367820133678353
ENSE000016673553368600433686385

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 89.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6683 / max 413.5667, expressed in 1440 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
18697012.66831440

Top tissues by expression

267 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
ganglionic eminenceUBERON:000402389.40gold quality
secondary oocyteCL:000065589.18gold quality
ventricular zoneUBERON:000305388.37gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099185.60gold quality
oocyteCL:000002385.01gold quality
embryoUBERON:000092283.65gold quality
endometrium epitheliumUBERON:000481183.59gold quality
mucosa of transverse colonUBERON:000499180.76gold quality
stromal cell of endometriumCL:000225579.72gold quality
olfactory bulbUBERON:000226478.62gold quality
type B pancreatic cellCL:000016978.39gold quality
prefrontal cortexUBERON:000045178.08gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047377.87gold quality
bone marrowUBERON:000237177.69gold quality
tendon of biceps brachiiUBERON:000818877.64gold quality
lower esophagus mucosaUBERON:003583477.18gold quality
putamenUBERON:000187475.47gold quality
male germ cellCL:000001575.28gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451175.23gold quality
vena cavaUBERON:000408775.17gold quality
C1 segment of cervical spinal cordUBERON:000646975.06gold quality
triceps brachiiUBERON:000150974.98gold quality
lymph nodeUBERON:000002974.95gold quality
right adrenal gland cortexUBERON:003582774.82gold quality
spermCL:000001974.78gold quality
frontal cortexUBERON:000187074.54gold quality
cervix squamous epitheliumUBERON:000692274.53gold quality
gluteal muscleUBERON:000200074.52gold quality
right adrenal glandUBERON:000123374.45gold quality
right testisUBERON:000453474.42gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-MTAB-10662yes109.44
E-ANND-3no2.68

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

493 targets.

TargetRegulation
ABCA1Unknown
ABCB1Activation
ABCG2Unknown
ACANRepression
ACSL1Unknown
ACTR2Unknown
ADAM2
ADH6Unknown
AK3Unknown
ALG5
ALOX5APUnknown
AMPD3Unknown
ANGPT2Activation
ANKRD16Unknown
APAF1Activation
ARActivation
ARHGEF17Unknown
ARL10Unknown
ARMC8Unknown
ASCC2Unknown
ASF1BActivation
ATAD2Unknown
ATG10Activation
ATG12Activation
ATG4AActivation
ATG4BActivation
ATG4DActivation
ATG5Activation
ATG7Activation
ATG9AActivation

JASPAR motifs

MotifNameFamily
MA0024.1E2F1E2F
MA0024.2E2F1E2F
MA0024.3E2F1E2F

JASPAR matrix evidence (PMIDs): PMID:1411535, PMID:17908821, PMID:9372931

Upstream regulators (CollecTRI, top): ARID3A, ATM, CTNNB1, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, E2F7, E2F8, ELL, ERCC2, ESR1, FOS, FOXC1, FOXJ3, GLI2, HCFC1, HDAC1, HES1, HES6, HIC1, IRF1, KLF15, KMT2E, LEF1, MECOM, MYBL2, MYC, MYOD1, NANOG, NFKB1, NFKB, NFYA, NKX2-5, NKX6-1, NR0B2, NR2F2, NR4A1

miRNA regulators (miRDB)

66 targeting E2F1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-8485100.0077.574731
HSA-MIR-5692A100.0074.406850
HSA-MIR-6748-5P100.0065.811057
HSA-MIR-9-3P99.9670.882068
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-329-3P99.9166.561234
HSA-MIR-362-3P99.9166.381267
HSA-MIR-106A-5P99.9073.942683
HSA-MIR-17-5P99.8973.832665
HSA-MIR-95-5P99.8972.173973
HSA-MIR-106B-5P99.8874.722795
HSA-MIR-20A-5P99.8874.762769
HSA-MIR-20B-5P99.8874.012621
HSA-MIR-519D-3P99.8873.972607
HSA-MIR-93-5P99.8873.982606
HSA-MIR-526B-3P99.8874.062587
HSA-MIR-3140-3P99.8868.472069
HSA-MIR-477999.8666.501583
HSA-MIR-394199.8670.542735
HSA-MIR-205-5P99.8170.051557
HSA-MIR-320A-3P99.7769.732107
HSA-MIR-320B99.7769.732107
HSA-MIR-320C99.7769.732107
HSA-MIR-320D99.7769.732107
HSA-MIR-442999.7769.622111
HSA-MIR-378G99.7164.901106
HSA-MIR-519A-3P99.6771.671868
HSA-MIR-519B-3P99.6771.671868
HSA-MIR-519C-3P99.6771.671870
HSA-MIR-6887-3P99.6667.831778

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

  • transcriptional inhibition of the plasminogen activator inhibitor type 1 gene (PMID:11559366)
  • expression reduced in primary and metastatic breast carcinoma (PMID:11759817)
  • selection and characterization of active hammerhead ribozymes targeted against E2F1 full-length mRNA (PMID:11763345)
  • Regulation of E2F1-dependent gene transcription and apoptosis by the ETS-related transcription factor GABPgamma1 (PMID:11884602)
  • increased ppRb and E2FI immunoreactivity in Alzheimer disease brain, with ppRb predominately located in the nucleus and E2F1 in the cytoplasm. (PMID:11939591)
  • Human telomerase accelerates growth of lens epithelial cells through regulation of the genes mediating RB/E2F pathway. (PMID:12032846)
  • Overexpression of E2F-1 induces apoptosis and increases chemosensitivity in human pancreatic carcinoma cells. Cell cycle, PARP cleavage and morphology supported apoptosis as the cell death mechanism in reponse to E2F1. (PMID:12065845)
  • conclude that E2F proteins and Sp1 play an important role in the control of p18 expression (PMID:12077144)
  • p14(ARF) regulates E2F activity in different cell types and down-regulates E2F-dependent transcription, and in cells undergoing E2F-dependent apoptosis prompts cell cycle arrest. p14(ARF) possesses multiple binding domains for E2F-1. (PMID:12082609)
  • p73beta is transcriptionally induced by E2F-1 and functions as a positive regulator of apoptosis. (PMID:12095638)
  • Most of the TGF-beta1-induced preapoptotic cells were arrested in G(1) phase of the cell cycle. This was associated with a significant increase in both E2F-DNA-binding activity and transcription of E2F-responsive reporter constructs. (PMID:12118073)
  • E2F-1 regulates the expression of APAF-1 in human cells (PMID:12149244)
  • E2F-1 has a role in regulation of caspase proenzymes through a direct transcriptional mechanism (PMID:12389032)
  • Che-1 contacts the pocket region of Rb and removes HDAC1 from the Rb/E2F1 complex, affecting the activation of E2F-dependent promoters and cell division. (PMID:12450794)
  • During thyroid hormone-induced differentiation of embryonic carcinoma cells and of oligodendrocyte precursor cells, levels of E2F-1 mRNA and E2F-1 protein decrease, caused by thyroid hormone receptor regulating the transcription of the E2F-1 gene. (PMID:12511608)
  • IFN-gamma is an effective inhibitor of ASM cell proliferation by blocking transition from G1-to-S phase by acting at two different levels: modulation of cdk2/cyclin E activation and inhibition of E2F-1 gene expression. (PMID:12588705)
  • expression of the transcription factor DP-1 and its heterodimeric partner E2F-1 in non-Hodgkin lymphoma (PMID:12607600)
  • We found that E2F1 was present at most of the CpG islands bound by pRb, independent of the phase of the cell cycle, our data suggest that the majority of DNA-bound pRb is recruited to E2F target promoters during both G(0)/G(1) and S phases. (PMID:12629508)
  • P202 inhibits E2F1-mediated apoptosis in prostate cancer cells (PMID:12646190)
  • E2F1 is involved in heat shock-induced cell cycle arrests at the G1/S and G2/M checkpoints, which also may be relevant for hyperthermic cancer therapy (PMID:12674510)
  • esf-1 induces apoptosis and inhibits proliferation of human colon cancer cell lines; a caspase-independent pathway is suggested (PMID:12679318)
  • Chk2 phosphorylates and activates E2F-1 in response to DNA damage, resulting in apoptosis. This suggests a role for E2F-1 in checkpoint control and tumour suppression. (PMID:12717439)
  • In response to DNA damage, E2F1 is directed from cell cycle progression to apoptotic E2F target genes. (PMID:12766778)
  • Analysis of gene expression level profiles showed that parental cell line undergoes apoptosis through an E2F1/p73-dependent pathway while its drug resistant variant evades it. (PMID:12789260)
  • Both senescence-associated heterochromatin foci formation and the silencing of E2F target genes depend on the integrity of the Rb pathway and do not occur in reversibly arrested cells (PMID:12809602)
  • C/EBPepsilon interacts with Rb and E2F1 during granulocytic differentiation (PMID:12947005)
  • E2F1 is upregulated by TR3 orphan nuclear receptor in human prostate cancer cells (PMID:12947120)
  • the Cyclin D1/E2F1 pathway may be involved in apoptotic death of bone marrow cells in myelodysplastic syndromes (PMID:12965081)
  • E2F1 activity is repressed by BRG1, but this repression is blocked when BRG1 interacts with EVI1 (PMID:14555651)
  • two E2F-binding sites play distinct roles in the regulation of E2F1 transcription by interacting with different sets of E2F members and cooperating with the contiguous repressor element (PMID:14576826)
  • Here we show that the E2F1 binding domain of prohibitin has the potential to fold into a coiled-coil structure. (PMID:14637159)
  • E2F and Sp1/Sp3 synergize but are not sufficient to activate the MYCN gene in neuroblastoma (PMID:14645238)
  • results establish that tumor necrosis factor alpha targets insulin-like growth factor-I induced E2F-transcription facor 1 synthesis, leading to inhibition of accumulation in cyclin A and hyperphosphorylation of RB protein (PMID:14681231)
  • E2F1 transactivation is repressed by MdmX (PMID:14739777)
  • Our results suggest that overexpression of E2F1, induced both by LOH at the RB locus and anomalous phosphorylation of the RB protein, is involved in the development of non-small cell lung carcinoma. (PMID:14997382)
  • Results suggest that E2F1 plays a central role in signaling disturbances in the retinoblastoma growth control pathway and, by upregulation of Chk2 by Atm and Nbs1, may sensitize cells to undergo apoptosis. (PMID:15024084)
  • The data suggest that E2F-1 overexpression plays a role in suppression of tumor, at least in part trough transcriptional regulation of FHIT and relevant activation of WWOX. (PMID:15044096)
  • ErbB3-binding protein Ebp1 binding to E2F promoter elements and E2F-mediated transcription are regulated by heregulin (PMID:15073182)
  • increased expression of the E2F1 gene might play a significant role in human thyroid carcinogenesis through derangement of the Rb-E2F signaling pathway (PMID:15118916)
  • E2F1-dependent recruitment of Tip60 to chromatin occurred in late G(1) (PMID:15121871)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_rerioe2f1ENSDARG00000103868
mus_musculusE2f1ENSMUSG00000027490
rattus_norvegicusE2f1ENSRNOG00000072439
caenorhabditis_elegansWBGENE00009899

Paralogs (7): E2F2 (ENSG00000007968), E2F3 (ENSG00000112242), E2F8 (ENSG00000129173), E2F5 (ENSG00000133740), E2F7 (ENSG00000165891), E2F6 (ENSG00000169016), E2F4 (ENSG00000205250)

Protein

Protein identifiers

Transcription factor E2F1Q01094 (reviewed: Q01094)

Alternative names: PBR3, Retinoblastoma-associated protein 1, Retinoblastoma-binding protein 3, pRB-binding protein E2F-1

All UniProt accessions (1): Q01094

UniProt curated annotations — full annotation on UniProt →

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. E2F1 binds preferentially RB1 in a cell-cycle dependent manner. It can mediate both cell proliferation and TP53/p53-dependent apoptosis. Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters. Directly activates transcription of PEG10. Positively regulates transcription of RRP1B.

Subunit / interactions. Component of the DRTF1/E2F transcription factor complex. Forms heterodimers with DP family members. The E2F1 complex binds specifically hypophosphorylated RB1, the interaction represses E2F1-driven transcription. During the cell cycle, RB1 becomes phosphorylated in mid-to-late G1 phase, detaches from the DRTF1/E2F complex, rendering E2F transcriptionally active. Viral oncoproteins, notably E1A, T-antigen and HPV E7, are capable of sequestering RB1, thus releasing the active complex. Interacts with TRRAP, which probably mediates its interaction with histone acetyltransferase complexes, leading to transcription activation. Binds TOPBP1 and EAPP. Interacts with ARID3A. Interacts with TRIM28; the interaction inhibits E2F1 acetylation through recruiting HDAC1 and represses its transcriptional activity. Interaction with KAT2B; the interaction acetylates E2F1 enhancing its DNA-binding and transcriptional activity. Interacts with BIRC2/c-IAP1 (via BIR domains). The complex TFDP1:E2F1 interacts with CEBPA; the interaction prevents CEBPA binding to target genes promoters and represses its transcriptional activity. Interacts with RRP1B. Interacts with HCFC1. Interacts with KMT2E; the interaction is probably indirect and is mediated via HCFC1. Interacts with DCAF5 and L3MBTL3; the interaction requires methylation at Lys-185 and is necessary to target E2F1 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL123.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase. Phosphorylation at Ser-364 by CHEK2 stabilizes E2F1 upon DNA damage and regulates its effect on transcription and apoptosis. Phosphorylation at Ser-403 by GSK3B promotes interaction with USP11, leading to its deubiquitination and stabilization. Ubiquitinated via ‘Lys-63’-linked ubiquitin, leading to its degradation. Deubiquitinated by USP11 following phosphorylation by GSK3B, promoting its stability. Acetylation stimulates DNA-binding. Enhanced under stress conditions such as DNA damage and inhibited by retinoblastoma protein RB1. Regulated by KAP1/TRIM28 which recruits HDAC1 to E2F1 resulting in deacetylation. Acetylated by P/CAF/KAT2B. Methylation at Lys-185 by SETD7 promotes E2F1 ubiquitin-dependent proteasomal degradation.

Activity regulation. BIRC2/c-IAP1 stimulates its transcriptional activity.

Similarity. Belongs to the E2F/DP family.

RefSeq proteins (1): NP_005216* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR003316E2F_WHTH_DNA-bd_domDomain
IPR015633E2FFamily
IPR032198E2F_CC-MBDomain
IPR036388WH-like_DNA-bd_sfHomologous_superfamily
IPR036390WH_DNA-bd_sfHomologous_superfamily
IPR037241E2F-DP_heterodimHomologous_superfamily

Pfam: PF02319, PF16421

UniProt features (51 total): region of interest 10, mutagenesis site 9, modified residue 8, strand 6, sequence variant 5, sequence conflict 4, helix 4, chain 1, DNA-binding region 1, short sequence motif 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDBMethodResolution (Å)
6G0PX-RAY DIFFRACTION1.3
5M9OX-RAY DIFFRACTION1.45
6ULSX-RAY DIFFRACTION1.5
5M9NX-RAY DIFFRACTION1.95
1H24X-RAY DIFFRACTION2.5
2AZEX-RAY DIFFRACTION2.55
1O9KX-RAY DIFFRACTION2.6
9CB3ELECTRON MICROSCOPY3.47

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q01094-F163.400.24

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 117, 120, 125, 185, 364, 375, 403, 433

Mutagenesis-validated functional residues (9):

PositionPhenotype
117abolishes acetylation; when associated with r-120 and r-125.
120abolishes acetylation; when associated with r-117 and r-125.
125abolishes acetylation; when associated with r-117 and r-120.
132abolishes interaction with and repression of cebpa and inhibition of adipogenesis.
185abrogates methylation by setd7. loss of interaction with l3mbtl3. loss of ubiquitination by the crl4-dcaf5 e3 ubiquitin
364abrogates in vitro phosphorylation by chek2 and chek2-dependent stabilization of e2f1 upon dna damage.
403decreased phosphorylation by gsk3b, leading to abolished interaction with usp11 and subsequent deubiquitination.
411no retinoblastoma protein binding. no effect on interaction with and repression of cebpa.
433decreased phosphorylation by gsk3b.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

IDPathway
R-HSA-111448Activation of NOXA and translocation to mitochondria
R-HSA-113501Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-1362277Transcription of E2F targets under negative control by DREAM complex
R-HSA-1362300Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-139915Activation of PUMA and translocation to mitochondria
R-HSA-1912408Pre-NOTCH Transcription and Translation
R-HSA-2559580Oxidative Stress Induced Senescence
R-HSA-2559585Oncogene Induced Senescence
R-HSA-6804116TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-HSA-68911G2 Phase
R-HSA-69202Cyclin E associated events during G1/S transition
R-HSA-69205G1/S-Specific Transcription
R-HSA-69231Cyclin D associated events in G1
R-HSA-69656Cyclin A:Cdk2-associated events at S phase entry
R-HSA-8953750Transcriptional Regulation by E2F6
R-HSA-9616222Transcriptional regulation of granulopoiesis
R-HSA-9661069Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)

MSigDB gene sets: 659 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, RNGTGGGC_UNKNOWN, E2F_Q4, REACTOME_INHIBITION_OF_REPLICATION_INITIATION_OF_DAMAGED_DNA_BY_RB1_E2F1, REACTOME_SIGNALING_BY_NOTCH, MODULE_52, E2F_Q4_01, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, HNF3ALPHA_Q6, PAX4_01, PID_TELOMERASE_PATHWAY, E2F4DP1_01

GO Biological Process (31): DNA damage checkpoint signaling (GO:0000077), negative regulation of transcription by RNA polymerase II (GO:0000122), DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), spermatogenesis (GO:0007283), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), positive regulation of gene expression (GO:0010628), quinolinate biosynthetic process (GO:0019805), forebrain development (GO:0030900), response to lipopolysaccharide (GO:0032496), positive regulation of apoptotic process (GO:0043065), anoikis (GO:0043276), negative regulation of DNA binding (GO:0043392), negative regulation of fat cell differentiation (GO:0045599), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of fibroblast proliferation (GO:0048146), mRNA stabilization (GO:0048255), positive regulation of glial cell proliferation (GO:0060252), negative regulation of fat cell proliferation (GO:0070345), cellular response to fatty acid (GO:0071398), cellular response to hypoxia (GO:0071456), cellular response to xenobiotic stimulus (GO:0071466), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), lens fiber cell apoptotic process (GO:1990086), cellular response to nerve growth factor stimulus (GO:1990090), regulation of G1/S transition of mitotic cell cycle (GO:2000045), apoptotic process (GO:0006915), regulation of cell cycle (GO:0051726)

GO Molecular Function (14): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription activator activity (GO:0001216), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein kinase binding (GO:0019901), sequence-specific DNA binding (GO:0043565), protein dimerization activity (GO:0046983), molecular adaptor activity (GO:0060090), DNA-binding transcription factor binding (GO:0140297), sequence-specific double-stranded DNA binding (GO:1990837), transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515)

GO Cellular Component (10): nuclear chromosome (GO:0000228), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), protein-containing complex (GO:0032991), Rb-E2F complex (GO:0035189), RNA polymerase II transcription regulator complex (GO:0090575), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-13 pathways:

CategoryPathways
Activation of BH3-only proteins2
G0 and Early G12
Cellular Senescence2
G1/S Transition2
E2F mediated regulation of DNA replication1
Pre-NOTCH Expression and Processing1
TP53 Regulates Transcription of Cell Cycle Genes1
Mitotic G2-G2/M phases1
G1 Phase1
S Phase1
Generic Transcription Pathway1
Developmental Biology1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
regulation of DNA-templated transcription4
regulation of transcription by RNA polymerase II3
transcription by RNA polymerase II3
DNA-templated transcription3
transcription cis-regulatory region binding3
cellular anatomical structure3
gene expression2
regulation of gene expression2
apoptotic process2
DNA binding2
positive regulation of DNA-templated transcription2
RNA polymerase II transcription regulatory region sequence-specific DNA binding2
DNA-binding transcription factor activity2
binding2
chromosome2
nuclear lumen2
DNA integrity checkpoint signaling1
signal transduction in response to DNA damage1
negative regulation of DNA-templated transcription1
RNA biosynthetic process1
regulation of RNA biosynthetic process1
developmental process involved in reproduction1
male gamete generation1
DNA damage response1
intrinsic apoptotic signaling pathway1
positive regulation of macromolecule biosynthetic process1
dicarboxylic acid biosynthetic process1
quinolinate metabolic process1
pyridine-containing compound biosynthetic process1
brain development1
anatomical structure development1
response to molecule of bacterial origin1
response to lipid1
response to oxygen-containing compound1
regulation of apoptotic process1
positive regulation of programmed cell death1
negative regulation of binding1
regulation of DNA binding1
fat cell differentiation1
negative regulation of cell differentiation1

Protein interactions and networks

STRING

4508 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
E2F1RB1P06400996
E2F1FOXO3O43524995
E2F1TFDP1Q14186994
E2F1HDAC1Q13547992
E2F1MYCP01106990
E2F1CCNA2P20248989
E2F1CCNA1P78396985
E2F1MDM2Q00987981
E2F1TP53P04637974
E2F1CDKN1AP38936947
E2F1TOPBP1Q92547946
E2F1DNMT1P26358945
E2F1NDNQ99608937
E2F1CDKN2AP42771921
E2F1HCFC1P51610919

IntAct

186 interactions, top by confidence:

ABTypeScore
RB1E2F1psi-mi:“MI:0915”(physical association)0.980
E2F1RB1psi-mi:“MI:0407”(direct interaction)0.980
E2F1RB1psi-mi:“MI:0915”(physical association)0.980
E2F1RB1psi-mi:“MI:0914”(association)0.980
RB1E2F1psi-mi:“MI:0407”(direct interaction)0.980

BioGRID (492): E2F1 (Reconstituted Complex), RB1 (Affinity Capture-Western), E2F1 (Affinity Capture-RNA), E2F1 (Affinity Capture-RNA), E2F1 (Two-hybrid), E2F1 (Affinity Capture-Western), KAT2B (Affinity Capture-Western), E2F1 (Affinity Capture-Western), CREBBP (Reconstituted Complex), E2F1 (Affinity Capture-Western), E2F1 (Affinity Capture-Western), E2F1 (Affinity Capture-Western), E2F1 (Affinity Capture-Western), E2F1 (Affinity Capture-Western), TFDP1 (Affinity Capture-Western)

ESM2 similar proteins: A0JMD2, A5D7E9, A6NMN3, A7XW16, F1QDF8, F1RDM5, O00716, O09139, O35261, O35668, O42367, O43151, O54968, P14607, P59054, P59598, P97691, Q00175, Q01094, Q08050, Q14209, Q14494, Q16254, Q4V8F1, Q5DU28, Q5NUA6, Q5RA25, Q5W1J6, Q5ZL67, Q60664, Q60795, Q61321, Q61501, Q61985, Q63449, Q66IG8, Q6DJE5, Q6JPI3, Q76N89, Q7TS75

Diamond homologs: A0AVK6, A5HWA8, D4A4D7, E1BE02, E1BKK0, F1LMN3, F1QZ88, F6YVB9, F7EA39, O00716, O35261, O54917, O75461, P56931, Q01094, Q08DY6, Q14209, Q15329, Q16254, Q20619, Q27368, Q58FA4, Q5RIX9, Q61501, Q61502, Q62814, Q6DE14, Q6S7F2, Q8LSZ4, Q8R0K9, Q8RWL0, Q90977, Q96AV8, Q9FNY0, Q9FV70, Q9FV71, Q9LFQ9, O09139, O77051

SIGNOR signaling

72 interactions.

AEffectBMechanism
CHEK2“up-regulates quantity by stabilization”E2F1phosphorylation
MAPK3up-regulatesE2F1phosphorylation
CDK8down-regulatesE2F1phosphorylation
HES1“down-regulates quantity by repression”E2F1“transcriptional regulation”
HES6“up-regulates quantity by expression”E2F1“transcriptional regulation”
E2F1“up-regulates quantity by expression”ATM“transcriptional regulation”
E2F1up-regulatesHDAC1binding
E2F1“form complex”SMAD7/HDAC1/E2F-1binding
HDAC3up-regulatesE2F1binding
E2F1up-regulatesPPARG“transcriptional regulation”
ERK1/2“up-regulates activity”E2F1phosphorylation
E2F1“up-regulates quantity by expression”CDC25A“transcriptional regulation”
E2F1“up-regulates quantity by expression”CyclinE/CDK2“transcriptional regulation”
E2F1“up-regulates quantity by expression”CCNE1“transcriptional regulation”
E2F1up-regulatesG1/S_transition
E2F1“up-regulates quantity by expression”ABCB1“transcriptional regulation”
E2F1“up-regulates quantity by expression”BBC3“transcriptional regulation”
E2F1“up-regulates quantity by expression”HIC1“transcriptional regulation”
E2F1“down-regulates quantity by repression”HSPA5“transcriptional regulation”
E2F1“up-regulates quantity by expression”LRBA“transcriptional regulation”
E2F1“up-regulates quantity by expression”MCPH1“transcriptional regulation”
E2F1“up-regulates quantity by expression”ELF4“transcriptional regulation”
E2F1“up-regulates quantity by expression”RASGRP1“transcriptional regulation”
E2F1“up-regulates quantity by expression”RASGEF1B“transcriptional regulation”
E2F1“up-regulates quantity by expression”RRM1“transcriptional regulation”
E2F1“up-regulates quantity by expression”DHFR“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)561.0×8e-07
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest557.8×1e-06
Transcription of E2F targets under negative control by DREAM complex552.3×2e-06
Oncogene Induced Senescence851.7×1e-09
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer642.5×4e-07
G0 and Early G1542.2×4e-06
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription741.5×3e-08
G1/S-Specific Transcription641.2×4e-07

GO biological processes:

GO termPartnersFoldFDR
cellular response to insulin stimulus616.5×2e-04
chromatin remodeling1011.8×3e-06
negative regulation of cell growth511.6×3e-03
regulation of cell cycle910.8×2e-05
negative regulation of gene expression77.8×2e-03
DNA damage response86.9×1e-03
transcription by RNA polymerase II66.8×7e-03
positive regulation of apoptotic process76.4×4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

57 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance35
Likely benign8
Benign9

Top pathogenic / likely-pathogenic (0)

SpliceAI

1707 predictions. Top by Δscore:

VariantEffectΔscore
10:47353372:G:GCacceptor_gain1.0000
10:47353514:C:CTdonor_loss1.0000
10:47353515:A:ATdonor_loss1.0000
10:47353516:GAC:Gdonor_loss1.0000
10:47353517:TGAC:Tdonor_loss1.0000
10:47355518:ACC:Adonor_loss1.0000
10:47355520:GTA:Gdonor_loss1.0000
10:47355521:CGTA:Cdonor_loss1.0000
20:33676980:C:CCacceptor_gain1.0000
20:33677102:CACC:Cdonor_loss1.0000
20:33677327:AGTT:Aacceptor_gain1.0000
20:33677420:TCTCA:Tdonor_loss1.0000
20:33677421:CTCA:Cdonor_loss1.0000
20:33677422:TCAC:Tdonor_loss1.0000
20:33677423:CA:Cdonor_loss1.0000
20:33677424:A:Tdonor_loss1.0000
20:33677425:C:CTdonor_loss1.0000
20:33678216:T:TAdonor_gain1.0000
20:33678235:G:Cdonor_gain1.0000
20:33678349:TGCCC:Tacceptor_gain1.0000
20:33678350:GCCC:Gacceptor_gain1.0000
20:33678351:CCC:Cacceptor_gain1.0000
20:33678351:CCCC:Cacceptor_gain1.0000
20:33678352:CC:Cacceptor_gain1.0000
20:33678352:CCCTG:Cacceptor_gain1.0000
20:33678353:CCTG:Cacceptor_gain1.0000
20:33678354:C:CCacceptor_gain1.0000
20:33678354:C:CGacceptor_loss1.0000
20:33678355:T:Aacceptor_loss1.0000
20:33679753:A:ACdonor_gain1.0000

AlphaMissense

2804 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
20:33679764:A:TI188N1.000
20:33679769:G:CN186K1.000
20:33679769:G:TN186K1.000
20:33679772:C:AK185N1.000
20:33679772:C:GK185N1.000
20:33679774:T:CK185E1.000
20:33679781:C:AK182N1.000
20:33679781:C:GK182N1.000
20:33679783:T:CK182E1.000
20:33679788:A:TI180N1.000
20:33679791:A:GL179P1.000
20:33679801:C:GG176R1.000
20:33679806:A:GL174P1.000
20:33679806:A:TL174H1.000
20:33679809:A:TV173D1.000
20:33679811:G:CN172K1.000
20:33679811:G:TN172K1.000
20:33679813:T:CN172D1.000
20:33679818:A:CI170S1.000
20:33679818:A:TI170N1.000
20:33679820:G:CD169E1.000
20:33679820:G:TD169E1.000
20:33679821:T:AD169V1.000
20:33679821:T:CD169G1.000
20:33679821:T:GD169A1.000
20:33679822:C:AD169Y1.000
20:33679822:C:GD169H1.000
20:33679822:C:TD169N1.000
20:33679824:T:CY168C1.000
20:33679825:A:GY168H1.000

dbSNP variants (sampled 300 via entrez): RS1000130244 (20:33684356 C>T), RS1000295629 (20:33678601 T>C), RS1000518535 (20:33684056 C>G,T), RS1000962550 (20:33676496 C>T), RS1001002474 (20:33677017 C>T), RS1001124749 (20:33682922 T>C), RS1001462616 (20:33685678 C>T), RS1001505758 (20:33683354 G>C), RS1001567608 (20:33679398 G>T), RS1001619912 (20:33679093 T>C), RS1001726041 (20:33685896 C>T), RS1001773214 (20:33685431 T>C), RS1001794744 (20:33684443 C>A,G), RS1002056610 (20:33684687 T>C), RS1002205824 (20:33685673 G>A,C)

Disease associations

OMIM: gene MIM:189971 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): prostate cancer (MONDO:0008315), long QT syndrome (MONDO:0002442)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

StudyTraitp-value
GCST006979_538Heel bone mineral density1.000000e-19
GCST008839_103Height5.000000e-13
GCST012226_838Waist circumference adjusted for body mass index4.000000e-08

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0009270heel bone mineral density
EFO:0007789BMI-adjusted waist circumference

MeSH disease descriptors (2)

DescriptorNameTree numbers
D008133Long QT SyndromeC14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D011471Prostatic NeoplasmsC04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4382 (SINGLE PROTEIN), CHEMBL4630726 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

179 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
sodium arsenitedecreases reaction, increases expression, decreases expression, affects expression, affects reaction (+1 more)7
bisphenol Aaffects expression, increases expression, affects cotreatment6
Arsenic Trioxideaffects binding, decreases reaction, increases reaction, decreases expression, increases expression (+1 more)6
Benzo(a)pyreneincreases expression, increases methylation, increases reaction, decreases reaction, affects activity (+1 more)6
Estradioldecreases reaction, increases expression, affects reaction, affects expression, affects binding (+1 more)6
Tretinoindecreases reaction, increases expression, decreases expression6
Cannabidioldecreases expression, increases expression, affects cotreatment5
Doxorubicinaffects expression, affects binding, decreases reaction, increases expression, increases reaction (+3 more)4
Cadmium Chloridedecreases expression, increases expression, decreases reaction4
methylselenic acidaffects expression, affects binding, increases reaction, decreases expression3
(+)-JQ1 compoundaffects cotreatment, decreases expression, decreases activity3
Troglitazoneaffects cotreatment, decreases expression3
Aspirinaffects cotreatment, affects binding, decreases reaction, decreases expression3
Cisplatindecreases expression, increases acetylation, increases expression3
Copperaffects binding, decreases expression, increases expression3
Nicotinedecreases reaction, increases expression, affects binding, increases reaction3
Valproic Acidaffects expression, increases expression, increases methylation3
zinc chromatedecreases expression, affects localization, affects reaction, increases abundance2
cadmium acetateaffects binding, increases reaction, decreases activity, decreases expression, affects localization2
hydroquinoneincreases expression, increases reaction2
chromium hexavalent ionaffects localization, affects reaction, increases abundance, decreases expression2
alvocidibincreases expression, increases response to substance, decreases expression2
2,2’,4,4’-tetrabromodiphenyl etherincreases expression2
Gefitinibdecreases expression2
Acetaminophenincreases expression2
Arsenicdecreases expression, increases expression, affects reaction2
Chelating Agentsaffects binding, decreases expression, increases expression2
Oxygenaffects cotreatment, decreases expression2
Quercetinincreases expression2
Tamoxifenincreases expression, decreases expression, affects binding, increases reaction2

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL2445129BindingInduction of E2F1 ubiquitination in human A549 cells at 0.1 uM after 8 hrs by immunoprecipitation and Western blotting analysisLargazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of E2F1 in Lung Cancer Cells. — ACS Med Chem Lett

Cellosaurus cell lines

13 cell lines: 8 cancer cell line, 3 embryonic stem cell, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_A1B8SEES3-1V human E2F1, clone1Embryonic stem cellMale
CVCL_A1B9SEES3-1V human E2F1, clone2Embryonic stem cellMale
CVCL_A1C0SEES3-1V human E2F1, clone3Embryonic stem cellMale
CVCL_AW19K562 eGFP-E2F1Cancer cell lineFemale
CVCL_B1ASAbcam HEK293 E2F1 KOTransformed cell lineFemale
CVCL_B6FCHepZTransformed cell lineSex unspecified
CVCL_B8EYAbcam HCT 116 E2F1 KOCancer cell lineMale
CVCL_B8V1Abcam MCF-7 E2F1 KOCancer cell lineFemale
CVCL_B9H6Abcam A-549 E2F1 KOCancer cell lineMale
CVCL_HA20MCF-7/E2F1Cancer cell lineFemale

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT00029224PHASE4COMPLETEDTreatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997PHASE4COMPLETEDOpen-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609PHASE4COMPLETEDThe Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623PHASE4SUSPENDEDThe Plenaxis® Experience Study
NCT00106392PHASE4COMPLETEDA Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029PHASE4UNKNOWNMR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485PHASE4COMPLETEDAngelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219PHASE4COMPLETEDZoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271PHASE4COMPLETEDEffect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146PHASE4COMPLETEDStudy to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554PHASE4COMPLETEDOpen-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098PHASE4COMPLETEDDocetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696PHASE4COMPLETEDCasodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139PHASE4COMPLETEDEffect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765PHASE4COMPLETEDEffects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690PHASE4COMPLETEDEvaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708PHASE4COMPLETEDLocal Anesthesia for Prostate Biopsy
NCT00526331PHASE4COMPLETEDEvaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213PHASE4COMPLETEDCompare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330PHASE4TERMINATEDDissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966PHASE4COMPLETEDRadical Prostatectomy and Perioperative Fluid Therapy
NCT00805701PHASE4COMPLETEDStudy Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027PHASE4COMPLETEDEffect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269PHASE4UNKNOWNCan Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277PHASE4COMPLETEDStudy of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800PHASE4COMPLETEDDoes Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199PHASE4COMPLETEDGlobal Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226PHASE4COMPLETEDEvaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563PHASE4COMPLETEDRandomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905PHASE4COMPLETEDStudy to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672PHASE4COMPLETED3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143PHASE4TERMINATEDProspective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742PHASE4UNKNOWNComparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563PHASE4COMPLETEDHydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874PHASE4COMPLETEDEfficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472PHASE4TERMINATEDFirmagon (Degarelix) Intermittent Therapy
NCT01547416PHASE4COMPLETEDThe Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544PHASE4COMPLETEDThe Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749PHASE4UNKNOWNEvaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635PHASE4COMPLETEDStudy of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.