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Q16254 (E2F4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcription factor E2F4

Short name=E2F-4
Gene names
Name:E2F4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length413 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. E2F4 binds with high affinity to RBL1 and RBL2. In some instances can also bind RB1.

Subunit structure

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-4and isoform PML-5) Ref.1 Ref.2 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17

Subcellular location

Nucleus.

Tissue specificity

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

Developmental stage

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

Post-translational modification

Differentially phosphorylated in vivo.

Polymorphism

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.

Sequence similarities

Belongs to the E2F/DP family.

Ontologies

Keywords
   Biological processCell cycle
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblood circulation

Inferred from electronic annotation. Source: Ensembl

cell volume homeostasis

Inferred from electronic annotation. Source: Ensembl

cilium assembly

Inferred from electronic annotation. Source: Ensembl

epithelial cell development

Inferred from electronic annotation. Source: Ensembl

gene expression

Traceable author statement. Source: Reactome

mitotic cell cycle

Traceable author statement. Source: Reactome

organ morphogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Traceable author statement. Source: Reactome

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of cell size

Inferred from electronic annotation. Source: Ensembl

regulation of transcription involved in G1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription, DNA-templated

Traceable author statement. Source: Reactome

transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

transcription factor complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionDNA binding

Inferred from mutant phenotype Ref.11. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.11Ref.12Ref.13Ref.17. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction Ref.13. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.11. Source: UniProtKB

transcription factor binding

Inferred from physical interaction Ref.13. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

LIN9Q5TKA13EBI-448943,EBI-1389424

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.16
Chain2 – 413412Transcription factor E2F4
PRO_0000219468

Regions

DNA binding16 – 8570 Potential
Region43 – 6523Leucine-zipper
Region86 – 18196Dimerization Potential
Region337 – 41377Transactivation Potential
Region390 – 40718Interaction with RBL1 and RBL2 Potential
Motif48 – 8538DEF box
Motif389 – 3924HCFC1-binding-motif (HBM)
Compositional bias9 – 124Poly-Pro
Compositional bias307 – 32721Poly-Ser

Amino acid modifications

Modified residue21N-acetylalanine Ref.16

Natural variations

Natural variant2931T → P.
Corresponds to variant rs1801013 [ dbSNP | Ensembl ].
VAR_014936
Natural variant3191S → SSSS. Ref.1
VAR_014024

Secondary structure

............... 413
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16254 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: BAAC95DE1B7E0832

FASTA41343,960
        10         20         30         40         50         60 
MAEAGPQAPP PPGTPSRHEK SLGLLTTKFV SLLQEAKDGV LDLKLAADTL AVRQKRRIYD 

        70         80         90        100        110        120 
ITNVLEGIGL IEKKSKNSIQ WKGVGPGCNT REIADKLIEL KAEIEELQQR EQELDQHKVW 

       130        140        150        160        170        180 
VQQSIRNVTE DVQNSCLAYV THEDICRCFA GDTLLAIRAP SGTSLEVPIP EGLNGQKKYQ 

       190        200        210        220        230        240 
IHLKSVSGPI EVLLVNKEAW SSPPVAVPVP PPEDLLQSPS AVSTPPPLPK PALAQSQEAS 

       250        260        270        280        290        300 
RPNSPQLTPT AVPGSAEVQG MAGPAAEITV SGGPGTDSKD SGELSSLPLG PTTLDTRPLQ 

       310        320        330        340        350        360 
SSALLDSSSS SSSSSSSSSN SNSSSSSGPN PSTSFEPIKA DPTGVLELPK ELSEIFDPTR 

       370        380        390        400        410 
ECMSSELLEE LMSSEVFAPL LRLSPPPGDH DYIYNLDESE GVCDLFDVPV LNL 

« Hide

References

« Hide 'large scale' references
[1]"E2F-4, a new member of the E2F transcription factor family, interacts with p107."
Ginsberg D., Vairo G., Chittenden T., Xiao Z.-X., Xu G., Wydner K.L., Decaprio J.A., Lawrence J.B., Livingston D.M.
Genes Dev. 8:2665-2679(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-319 INS, INTERACTION WITH RBL1.
Tissue: Cervix carcinoma.
[2]"E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo."
Beijersbergen R.L., Kerkhoven R.M., Zhu L., Carlee L., Voorhoeve P.M., Bernards R.
Genes Dev. 8:2680-2690(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH RBL1.
Tissue: Colon carcinoma.
[3]"E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle."
Sardet C., Vidal M., Cobrinik D., Geng Y., Onufryk C., Chen A., Weinberg R.A.
Proc. Natl. Acad. Sci. U.S.A. 92:2403-2407(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Genomic structure and mutation screening of the E2F4 gene in human tumors."
Schwemmle S., Pfeifer G.P.
Int. J. Cancer 86:672-677(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]NIEHS SNPs program
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[10]"The predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4, DP-1 and p130."
Williams C.D., Linch D.C., Soerensen T.S., La Thangue N.B., Thomas N.S.B.
Br. J. Haematol. 96:688-696(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RBL2.
[11]"E2F transcriptional activation requires TRRAP and GCN5 cofactors."
Lang S.E., McMahon S.B., Cole M.D., Hearing P.
J. Biol. Chem. 276:32627-32634(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRRAP.
[12]"HCF-1 functions as a coactivator for the zinc finger protein Krox20."
Luciano R.L., Wilson A.C.
J. Biol. Chem. 278:51116-51124(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HCFC1.
[13]"Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release."
Rubin S.M., Gall A.-L., Zheng N., Pavletich N.P.
Cell 123:1093-1106(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WITH RB1; RBL1; TFDP1 AND TFDP2.
[14]"LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes."
Schmit F., Korenjak M., Mannefeld M., Schmitt K., Franke C., von Eyss B., Gagrica S., Haenel F., Brehm A., Gaubatz S.
Cell Cycle 6:1903-1913(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE DREAM COMPLEX.
[15]"Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence."
Litovchick L., Sadasivam S., Florens L., Zhu X., Swanson S.K., Velmurugan S., Chen R., Washburn M.P., Liu X.S., DeCaprio J.A.
Mol. Cell 26:539-551(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE DREAM COMPLEX.
[16]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[17]"Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence."
Martin N., Benhamed M., Nacerddine K., Demarque M.D., van Lohuizen M., Dejean A., Bischof O.
EMBO J. 31:95-109(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PML.
[18]"Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP."
Zheng N., Fraenkel E., Pabo C.O., Pavletich N.P.
Genes Dev. 13:666-674(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 11-86.
[19]"Various AGC repeat numbers in the coding region of the human transcription factor gene E2F-4."
Zhong X., Hemmi H., Koike J., Tsujita K., Shimatake H.
Hum. Mutat. 15:296-297(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: POLYMORPHISM.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS32464.1.
PIRA55237.
RefSeqNP_001941.2. NM_001950.3.
UniGeneHs.108371.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CF7X-ray2.60A11-86[»]
ProteinModelPortalQ16254.
SMRQ16254. Positions 16-82, 96-198.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108206. 59 interactions.
DIPDIP-24185N.
IntActQ16254. 20 interactions.
MINTMINT-88123.
STRING9606.ENSP00000368686.

PTM databases

PhosphoSiteQ16254.

Polymorphism databases

DMDM2494229.

Proteomic databases

MaxQBQ16254.
PaxDbQ16254.
PRIDEQ16254.

Protocols and materials databases

DNASU1874.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379378; ENSP00000368686; ENSG00000205250.
GeneID1874.
KEGGhsa:1874.
UCSCuc002erz.3. human.

Organism-specific databases

CTD1874.
GeneCardsGC16P067226.
HGNCHGNC:3118. E2F4.
HPACAB016523.
HPA054128.
MIM600659. gene.
neXtProtNX_Q16254.
PharmGKBPA27576.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG289227.
HOGENOMHOG000232045.
HOVERGENHBG002227.
InParanoidQ16254.
KOK04682.
OMAPHTLAYV.
OrthoDBEOG7WHHB1.
PhylomeDBQ16254.
TreeFamTF105566.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_71. Gene Expression.
SignaLinkQ16254.

Gene expression databases

ArrayExpressQ16254.
BgeeQ16254.
CleanExHS_E2F4.
GenevestigatorQ16254.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR015633. E2F.
IPR028312. E2F4.
IPR003316. E2F_TDP.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERPTHR12081. PTHR12081. 1 hit.
PTHR12081:SF42. PTHR12081:SF42. 1 hit.
PfamPF02319. E2F_TDP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ16254.
GeneWikiE2F4.
GenomeRNAi1874.
NextBio7659.
PROQ16254.
SOURCESearch...

Entry information

Entry nameE2F4_HUMAN
AccessionPrimary (citable) accession number: Q16254
Secondary accession number(s): A6NGR8 expand/collapse secondary AC list , B5BU56, Q12991, Q15328
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM