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Protein

Transcription factor E2F4

Gene

E2F4

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. E2F4 binds with high affinity to RBL1 and RBL2. In some instances can also bind RB1. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis.By similarity2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi16 – 8570Sequence analysisAdd
BLAST

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • promoter-specific chromatin binding Source: MGI
  • protein domain specific binding Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Cell cycle, Cilium biogenesis/degradation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-HSA-1538133. G0 and Early G1.
R-HSA-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-HSA-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
R-HSA-69231. Cyclin D associated events in G1.
SignaLinkiQ16254.
SIGNORiQ16254.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor E2F4
Short name:
E2F-4
Gene namesi
Name:E2F4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:3118. E2F4.

Subcellular locationi

GO - Cellular componenti

  • nuclear chromatin Source: BHF-UCL
  • nucleoplasm Source: HPA
  • transcription factor complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27576.

Polymorphism and mutation databases

BioMutaiE2F4.
DMDMi2494229.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 413412Transcription factor E2F4PRO_0000219468Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources
Modified residuei384 – 3841PhosphoserineCombined sources

Post-translational modificationi

Differentially phosphorylated in vivo.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ16254.
MaxQBiQ16254.
PaxDbiQ16254.
PeptideAtlasiQ16254.
PRIDEiQ16254.

PTM databases

iPTMnetiQ16254.
PhosphoSiteiQ16254.

Expressioni

Tissue specificityi

Found in all tissue examined including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Developmental stagei

Present in the growth-arrested state, its abundance does not change significantly as cells move into and through the cell cycle.

Gene expression databases

BgeeiENSG00000205250.
CleanExiHS_E2F4.
ExpressionAtlasiQ16254. baseline and differential.
GenevisibleiQ16254. HS.

Organism-specific databases

HPAiCAB016523.
HPA054128.

Interactioni

Subunit structurei

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. Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5). Interacts with CEBPA (when phosphorylated) (PubMed:15107404).10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
E7P031292EBI-448943,EBI-866453From a different organism.
LIN9Q5TKA13EBI-448943,EBI-1389424

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108206. 48 interactions.
DIPiDIP-24185N.
IntActiQ16254. 24 interactions.
MINTiMINT-88123.
STRINGi9606.ENSP00000368686.

Structurei

Secondary structure

1
413
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni17 – 204Combined sources
Helixi22 – 3514Combined sources
Beta strandi40 – 423Combined sources
Helixi43 – 497Combined sources
Turni50 – 523Combined sources
Helixi56 – 6813Combined sources
Beta strandi70 – 756Combined sources
Beta strandi78 – 814Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CF7X-ray2.60A11-86[»]
ProteinModelPortaliQ16254.
SMRiQ16254. Positions 16-82.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16254.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni43 – 6523Leucine-zipperAdd
BLAST
Regioni86 – 18196DimerizationSequence analysisAdd
BLAST
Regioni337 – 41377TransactivationSequence analysisAdd
BLAST
Regioni390 – 40718Interaction with RBL1 and RBL2Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi48 – 8538DEF boxAdd
BLAST
Motifi389 – 3924HCFC1-binding-motif (HBM)

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi9 – 124Poly-Pro
Compositional biasi307 – 32721Poly-SerAdd
BLAST

Sequence similaritiesi

Belongs to the E2F/DP family.Curated

Phylogenomic databases

eggNOGiKOG2577. Eukaryota.
ENOG410XNYI. LUCA.
GeneTreeiENSGT00550000074403.
HOGENOMiHOG000232045.
HOVERGENiHBG002227.
InParanoidiQ16254.
KOiK04682.
OMAiVQNSPHT.
OrthoDBiEOG091G0CJQ.
PhylomeDBiQ16254.
TreeFamiTF105566.

Family and domain databases

CDDicd14660. E2F_DD. 1 hit.
Gene3Di1.10.10.10. 1 hit.
InterProiIPR015633. E2F.
IPR028312. E2F4.
IPR032198. E2F_CC-MB.
IPR003316. E2F_WHTH_DNA-bd_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR12081. PTHR12081. 1 hit.
PTHR12081:SF42. PTHR12081:SF42. 1 hit.
PfamiPF16421. E2F_CC-MB. 1 hit.
PF02319. E2F_TDP. 1 hit.
[Graphical view]
SMARTiSM01372. E2F_TDP. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q16254-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEAGPQAPP PPGTPSRHEK SLGLLTTKFV SLLQEAKDGV LDLKLAADTL
60 70 80 90 100
AVRQKRRIYD ITNVLEGIGL IEKKSKNSIQ WKGVGPGCNT REIADKLIEL
110 120 130 140 150
KAEIEELQQR EQELDQHKVW VQQSIRNVTE DVQNSCLAYV THEDICRCFA
160 170 180 190 200
GDTLLAIRAP SGTSLEVPIP EGLNGQKKYQ IHLKSVSGPI EVLLVNKEAW
210 220 230 240 250
SSPPVAVPVP PPEDLLQSPS AVSTPPPLPK PALAQSQEAS RPNSPQLTPT
260 270 280 290 300
AVPGSAEVQG MAGPAAEITV SGGPGTDSKD SGELSSLPLG PTTLDTRPLQ
310 320 330 340 350
SSALLDSSSS SSSSSSSSSN SNSSSSSGPN PSTSFEPIKA DPTGVLELPK
360 370 380 390 400
ELSEIFDPTR ECMSSELLEE LMSSEVFAPL LRLSPPPGDH DYIYNLDESE
410
GVCDLFDVPV LNL
Length:413
Mass (Da):43,960
Last modified:November 1, 1997 - v2
Checksum:iBAAC95DE1B7E0832
GO

Polymorphismi

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti293 – 2931T → P.
Corresponds to variant rs1801013 [ dbSNP | Ensembl ].
VAR_014936
Natural varianti319 – 3191S → SSSS.
VAR_014024

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S75174 mRNA. Translation: AAB32597.1.
X86096 mRNA. Translation: CAA60050.2.
U15641 mRNA. Translation: AAC50119.1.
AF250378 Genomic DNA. Translation: AAF65226.1.
AB451292 mRNA. Translation: BAG70106.1.
AB451425 mRNA. Translation: BAG70239.1.
AF527540 Genomic DNA. Translation: AAM77918.1.
AC040160 Genomic DNA. No translation available.
CH471092 Genomic DNA. Translation: EAW83094.1.
BC033180 mRNA. Translation: AAH33180.1.
CCDSiCCDS32464.1.
PIRiA55237.
RefSeqiNP_001941.2. NM_001950.3.
UniGeneiHs.108371.

Genome annotation databases

EnsembliENST00000379378; ENSP00000368686; ENSG00000205250.
GeneIDi1874.
KEGGihsa:1874.
UCSCiuc002erz.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S75174 mRNA. Translation: AAB32597.1.
X86096 mRNA. Translation: CAA60050.2.
U15641 mRNA. Translation: AAC50119.1.
AF250378 Genomic DNA. Translation: AAF65226.1.
AB451292 mRNA. Translation: BAG70106.1.
AB451425 mRNA. Translation: BAG70239.1.
AF527540 Genomic DNA. Translation: AAM77918.1.
AC040160 Genomic DNA. No translation available.
CH471092 Genomic DNA. Translation: EAW83094.1.
BC033180 mRNA. Translation: AAH33180.1.
CCDSiCCDS32464.1.
PIRiA55237.
RefSeqiNP_001941.2. NM_001950.3.
UniGeneiHs.108371.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CF7X-ray2.60A11-86[»]
ProteinModelPortaliQ16254.
SMRiQ16254. Positions 16-82.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108206. 48 interactions.
DIPiDIP-24185N.
IntActiQ16254. 24 interactions.
MINTiMINT-88123.
STRINGi9606.ENSP00000368686.

PTM databases

iPTMnetiQ16254.
PhosphoSiteiQ16254.

Polymorphism and mutation databases

BioMutaiE2F4.
DMDMi2494229.

Proteomic databases

EPDiQ16254.
MaxQBiQ16254.
PaxDbiQ16254.
PeptideAtlasiQ16254.
PRIDEiQ16254.

Protocols and materials databases

DNASUi1874.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379378; ENSP00000368686; ENSG00000205250.
GeneIDi1874.
KEGGihsa:1874.
UCSCiuc002erz.4. human.

Organism-specific databases

CTDi1874.
GeneCardsiE2F4.
HGNCiHGNC:3118. E2F4.
HPAiCAB016523.
HPA054128.
MIMi600659. gene.
neXtProtiNX_Q16254.
PharmGKBiPA27576.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2577. Eukaryota.
ENOG410XNYI. LUCA.
GeneTreeiENSGT00550000074403.
HOGENOMiHOG000232045.
HOVERGENiHBG002227.
InParanoidiQ16254.
KOiK04682.
OMAiVQNSPHT.
OrthoDBiEOG091G0CJQ.
PhylomeDBiQ16254.
TreeFamiTF105566.

Enzyme and pathway databases

ReactomeiR-HSA-1538133. G0 and Early G1.
R-HSA-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-HSA-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
R-HSA-69231. Cyclin D associated events in G1.
SignaLinkiQ16254.
SIGNORiQ16254.

Miscellaneous databases

ChiTaRSiE2F4. human.
EvolutionaryTraceiQ16254.
GeneWikiiE2F4.
GenomeRNAii1874.
PROiQ16254.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000205250.
CleanExiHS_E2F4.
ExpressionAtlasiQ16254. baseline and differential.
GenevisibleiQ16254. HS.

Family and domain databases

CDDicd14660. E2F_DD. 1 hit.
Gene3Di1.10.10.10. 1 hit.
InterProiIPR015633. E2F.
IPR028312. E2F4.
IPR032198. E2F_CC-MB.
IPR003316. E2F_WHTH_DNA-bd_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR12081. PTHR12081. 1 hit.
PTHR12081:SF42. PTHR12081:SF42. 1 hit.
PfamiPF16421. E2F_CC-MB. 1 hit.
PF02319. E2F_TDP. 1 hit.
[Graphical view]
SMARTiSM01372. E2F_TDP. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiE2F4_HUMAN
AccessioniPrimary (citable) accession number: Q16254
Secondary accession number(s): A6NGR8
, B5BU56, Q12991, Q15328
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: September 7, 2016
This is version 171 of the entry and version 2 of the sequence. [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 16
    Human chromosome 16: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.