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Protein

Transcription factor E2F1

Gene

E2F1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:20176812).By similarity5 Publications

Enzyme regulationi

BIRC2/c-IAP1 stimulates its transcriptional activity.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi110 – 194Sequence analysisAdd BLAST85

GO - Molecular functioni

  • core promoter binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • protein dimerization activity Source: InterPro
  • protein kinase binding Source: Ensembl
  • sequence-specific DNA binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processApoptosis, Cell cycle, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-111448. Activation of NOXA and translocation to mitochondria.
R-HSA-113501. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
R-HSA-1362277. Transcription of E2F targets under negative control by DREAM complex.
R-HSA-1362300. Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1.
R-HSA-139915. Activation of PUMA and translocation to mitochondria.
R-HSA-1912408. Pre-NOTCH Transcription and Translation.
R-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-539107. Activation of E2F1 target genes at G1/S.
R-HSA-6804116. TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
R-HSA-68689. CDC6 association with the ORC:origin complex.
R-HSA-68911. G2 Phase.
R-HSA-69202. Cyclin E associated events during G1/S transition.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-69298. Association of licensing factors with the pre-replicative complex.
R-HSA-69656. Cyclin A:Cdk2-associated events at S phase entry.
R-MMU-539107. Activation of E2F1 target genes at G1/S.
SignaLinkiQ01094.
SIGNORiQ01094.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor E2F1
Short name:
E2F-1
Alternative name(s):
PBR3
Retinoblastoma-associated protein 1
Short name:
RBAP-1
Retinoblastoma-binding protein 3
Short name:
RBBP-3
pRB-binding protein E2F-1
Gene namesi
Name:E2F1
Synonyms:RBBP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:3113. E2F1.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: HPA
  • mitochondrion Source: GOC
  • nuclear chromatin Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • Rb-E2F complex Source: BHF-UCL

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi117K → R: Abolishes acetylation; when associated with R-120 and R-125. 1 Publication1
Mutagenesisi120K → R: Abolishes acetylation; when associated with R-117 and R-125. 1 Publication1
Mutagenesisi125K → R: Abolishes acetylation; when associated with R-117 and R-120. 1 Publication1
Mutagenesisi132L → E: Abolishes interaction with and repression of CEBPA and inhibition of adipogenesis. 1 Publication1
Mutagenesisi364S → A: Abrogates in vitro phosphorylation by CHEK2 and CHEK2-dependent stabilization of E2F1 upon DNA damage. 1 Publication1
Mutagenesisi411Y → C: No retinoblastoma protein binding. No effect on interaction with and repression of CEBPA. 2 Publications1

Organism-specific databases

DisGeNETi1869.
OpenTargetsiENSG00000101412.
PharmGKBiPA152.

Chemistry databases

ChEMBLiCHEMBL4382.

Polymorphism and mutation databases

BioMutaiE2F1.
DMDMi400928.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002194611 – 437Transcription factor E2F1Add BLAST437

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei117N6-acetyllysine1 Publication1
Modified residuei120N6-acetyllysine1 Publication1
Modified residuei125N6-acetyllysine1 Publication1
Modified residuei364Phosphoserine; by CHEK21 Publication1
Modified residuei375PhosphoserineCombined sources1

Post-translational modificationi

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.2 Publications
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.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ01094.
PaxDbiQ01094.
PeptideAtlasiQ01094.
PRIDEiQ01094.

PTM databases

iPTMnetiQ01094.
PhosphoSitePlusiQ01094.

Expressioni

Gene expression databases

BgeeiENSG00000101412.
CleanExiHS_E2F1.
GenevisibleiQ01094. HS.

Organism-specific databases

HPAiCAB000329.
CAB019308.
HPA008003.
HPA029735.

Interactioni

Subunit structurei

Component of the DRTF1/E2F transcription factor complex. Forms heterodimers with DP family members. The E2F1 complex binds specifically hypophosphorylated retinoblastoma protein RB1. 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 (PubMed:20176812). Interacts with human cytomegalovirus/HHV-5 protein UL123.By similarity11 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108201. 115 interactors.
DIPiDIP-24227N.
ELMiQ01094.
IntActiQ01094. 35 interactors.
MINTiMINT-112765.
STRINGi9606.ENSP00000345571.

Structurei

Secondary structure

1437
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi202 – 236Combined sources35
Helixi238 – 243Combined sources6
Beta strandi245 – 247Combined sources3
Helixi248 – 252Combined sources5
Turni257 – 259Combined sources3
Beta strandi260 – 266Combined sources7
Beta strandi272 – 277Combined sources6
Beta strandi282 – 287Combined sources6
Beta strandi289 – 291Combined sources3
Beta strandi294 – 296Combined sources3
Helixi421 – 424Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H24X-ray2.50E87-95[»]
1O9KX-ray2.60P/Q/R/S409-426[»]
2AZEX-ray2.55B200-301[»]
5M9NX-ray1.95C104-120[»]
5M9OX-ray1.45B108-116[»]
ProteinModelPortaliQ01094.
SMRiQ01094.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ01094.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni67 – 108Cyclin A:CDK2 binding1 PublicationAdd BLAST42
Regioni89 – 191Interaction with BIRC2/c-IAP11 PublicationAdd BLAST103
Regioni153 – 174Leucine-zipperAdd BLAST22
Regioni192 – 382Required for interaction with TRIM281 PublicationAdd BLAST191
Regioni195 – 284DimerizationSequence analysisAdd BLAST90
Regioni368 – 437TransactivationAdd BLAST70
Regioni409 – 426RB1 binding1 PublicationAdd BLAST18

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi158 – 194DEF boxAdd BLAST37

Sequence similaritiesi

Belongs to the E2F/DP family.Curated

Phylogenomic databases

eggNOGiKOG2577. Eukaryota.
ENOG410XNYI. LUCA.
GeneTreeiENSGT00550000074403.
HOGENOMiHOG000232045.
HOVERGENiHBG002227.
InParanoidiQ01094.
KOiK17454.
OMAiICTTQLR.
OrthoDBiEOG091G087U.
PhylomeDBiQ01094.
TreeFamiTF105566.

Family and domain databases

CDDicd14660. E2F_DD. 1 hit.
Gene3Di1.10.10.10. 1 hit.
InterProiView protein in InterPro
IPR015633. E2F.
IPR032198. E2F_CC-MB.
IPR003316. E2F_WHTH_DNA-bd_dom.
IPR011991. WHTH_DNA-bd_dom.
PANTHERiPTHR12081. PTHR12081. 1 hit.
PfamiView protein in Pfam
PF16421. E2F_CC-MB. 1 hit.
PF02319. E2F_TDP. 1 hit.
SMARTiView protein in SMART
SM01372. E2F_TDP. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.

Sequencei

Sequence statusi: Complete.

Q01094-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALAGAPAGG PCAPALEALL GAGALRLLDS SQIVIISAAQ DASAPPAPTG
60 70 80 90 100
PAAPAAGPCD PDLLLFATPQ APRPTPSAPR PALGRPPVKR RLDLETDHQY
110 120 130 140 150
LAESSGPARG RGRHPGKGVK SPGEKSRYET SLNLTTKRFL ELLSHSADGV
160 170 180 190 200
VDLNWAAEVL KVQKRRIYDI TNVLEGIQLI AKKSKNHIQW LGSHTTVGVG
210 220 230 240 250
GRLEGLTQDL RQLQESEQQL DHLMNICTTQ LRLLSEDTDS QRLAYVTCQD
260 270 280 290 300
LRSIADPAEQ MVMVIKAPPE TQLQAVDSSE NFQISLKSKQ GPIDVFLCPE
310 320 330 340 350
ETVGGISPGK TPSQEVTSEE ENRATDSATI VSPPPSSPPS SLTTDPSQSL
360 370 380 390 400
LSLEQEPLLS RMGSLRAPVD EDRLSPLVAA DSLLEHVRED FSGLLPEEFI
410 420 430
SLSPPHEALD YHFGLEEGEG IRDLFDCDFG DLTPLDF
Length:437
Mass (Da):46,920
Last modified:July 1, 1993 - v1
Checksum:i003B3F654F0C60DF
GO

Sequence cautioni

The sequence AAB24289 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti89 – 111KRRLD…PARGR → RTPGTPRRQRRLCPPRRPGR APC in AAD14150 (PubMed:7958836).CuratedAdd BLAST23
Sequence conflicti313S → Y in AAC50719 (PubMed:8964493).Curated1
Sequence conflicti322N → T in AAC50719 (PubMed:8964493).Curated1
Sequence conflicti329T → N in AAC50719 (PubMed:8964493).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048907200G → S. Corresponds to variant dbSNP:rs35385772Ensembl.1
Natural variantiVAR_013607252R → H1 PublicationCorresponds to variant dbSNP:rs3213172Ensembl.1
Natural variantiVAR_013608276V → M1 PublicationCorresponds to variant dbSNP:rs3213173Ensembl.1
Natural variantiVAR_013609311T → N1 PublicationCorresponds to variant dbSNP:rs3213174Ensembl.1
Natural variantiVAR_013610393G → S1 PublicationCorresponds to variant dbSNP:rs3213176Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M96577 mRNA. Translation: AAA35782.1.
U47677, U47675, U47676 Genomic DNA. Translation: AAC50719.1.
S49592 mRNA. Translation: AAB24289.1. Different initiation.
AF516106 Genomic DNA. Translation: AAM47604.1.
AL121906 Genomic DNA. No translation available.
BC050369 mRNA. Translation: AAH50369.1.
BC058902 mRNA. Translation: AAH58902.1.
S74230 Genomic DNA. Translation: AAD14150.1.
CCDSiCCDS13224.1.
PIRiJC4929.
RefSeqiNP_005216.1. NM_005225.2.
UniGeneiHs.654393.

Genome annotation databases

EnsembliENST00000343380; ENSP00000345571; ENSG00000101412.
GeneIDi1869.
KEGGihsa:1869.
UCSCiuc002wzu.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiE2F1_HUMAN
AccessioniPrimary (citable) accession number: Q01094
Secondary accession number(s): Q13143, Q92768
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: August 30, 2017
This is version 202 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families