Q16254 (E2F4_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 135.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Transcription factor E2F4 Short name=E2F-4 | ||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 | |
| 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
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 | |||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||
| 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
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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. 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. 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. 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
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 |
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| 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 Q15328 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| Human chromosome 16 Human chromosome 16: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with
