Q16254 (E2F4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor E2F4
Short name=E2F-4

Gene names

Name:

E2F4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	413 AA.
Sequence status	Complete.
Protein existence	Evidence 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-4 and isoform PML-5). Ref.1 Ref.2 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16
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 process	Cell cycle Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1 phase of mitotic cell cycle Traceable author statement. Source: Reactome blood circulation Inferred from electronic annotation. Source: Compara cell volume homeostasis Inferred from electronic annotation. Source: Compara cilium assembly Inferred from electronic annotation. Source: Compara epithelial cell development Inferred from electronic annotation. Source: Compara organ morphogenesis Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: Reactome regulation of cell proliferation Inferred from electronic annotation. Source: Compara regulation of cell size Inferred from electronic annotation. Source: Compara regulation of transcription involved in G1/S phase of mitotic cell cycle Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular_function	DNA binding Inferred from mutant phenotype Ref.11. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 413

413

Transcription factor E2F4

PRO_0000219468

Regions

DNA binding

16 – 85

70

Potential

Region

43 – 65

23

Leucine-zipper

Region

86 – 181

96

Dimerization Potential

Region

337 – 413

77

Transactivation Potential

Region

390 – 407

18

Interaction with RBL1 and RBL2 Potential

Motif

48 – 85

38

DEF box

Motif

389 – 392

4

HCFC1-binding-motif (HBM)

Compositional bias

9 – 12

4

Poly-Pro

Compositional bias

307 – 327

21

Poly-Ser

Natural variations

Natural variant

293

1

T → P.
Corresponds to variant rs1801013 [ dbSNP | Ensembl ].

VAR_014936

Natural variant

319

1

S → SSSS. Ref.1

VAR_014024

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

413

Helix Strand Turn

Details...

Turn

17 – 20

4

Helix

22 – 35

14

Beta strand

40 – 42

3

Helix

43 – 49

7

Turn

50 – 52

3

Helix

56 – 68

13

Beta strand

70 – 75

6

Beta strand

78 – 81

4

Sequences

	Sequence		Length	Mass (Da)
	Q16254 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: BAAC95DE1B7E0832	FASTA	413	43,960
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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.
[17]	"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.
[18]	"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.

Web resources

NIEHS-SNPs

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.

IPI

IPI00292880.

PIR

A55237.

RefSeq

NP_001941.2. NM_001950.3.

UniGene

Hs.108371.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CF7	X-ray	2.60	A	11-86	[»]

ProteinModelPortal

Q16254.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24185N.

IntAct

Q16254. 11 interactions.

MINT

MINT-88123.

STRING

9606.ENSP00000368686.

PTM databases

PhosphoSite

Q16254.

Polymorphism databases

DMDM

2494229.

Proteomic databases

PaxDb

Q16254.

PRIDE

Q16254.

Protocols and materials databases

DNASU

1874.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379378; ENSP00000368686; ENSG00000205250.

GeneID

1874.

KEGG

hsa:1874.

UCSC

uc002erz.3. human.

Organism-specific databases

CTD

1874.

GeneCards

GC16P067226.

HGNC

HGNC:3118. E2F4.

HPA

CAB016523.

MIM

600659. gene.

neXtProt

NX_Q16254.

PharmGKB

PA27576.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG289227.

HOGENOM

HOG000232045.

HOVERGEN

HBG002227.

InParanoid

Q16254.

KO

K04682.

OMA

PHTLAYV.

OrthoDB

EOG4S1T7H.

Enzyme and pathway databases

Pathway_Interaction_DB

smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.

Reactome

REACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q16254.

Bgee

Q16254.

CleanEx

HS_E2F4.

Genevestigator

Q16254.

GermOnline

ENSG00000205250. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.

InterPro

IPR015633. E2F.
IPR003316. E2F_TDP.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

PANTHER

PTHR12081. PTHR12081. 1 hit.

Pfam

PF02319. E2F_TDP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q16254.

GenomeRNAi

1874.

NextBio

7659.

SOURCE

Search...

Entry information

Entry name

E2F4_HUMAN

Accession

Primary (citable) accession number: Q16254
Secondary accession number(s): A6NGR8 , B5BU56, Q12991, Q15328

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 135 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.