| Description | In humans, E2F6 has 8 exons that span 20881 bp of genomic sequence. It has an ORF of 843 nt. |
| Transcription | There have been 5 mRNA splice variants identified in humans. Transcript variant 1 is the predominant transcript, and it encodes the longest mRNA isoform (a), which is 2342 bp. Transcript variant 2 contains an additional segment (2413 bp mRNA), compared to variant 1, that causes a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform b) is much shorter than isoform a. Transcript variants 2 and 4 encode isoform b. Transcript variant 3 lacks a segment (2287 bp mRNA), compared to variant 1, that causes a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform c) is much shorter than isoform a. Transcript variant 4 contains two additional segments (2546 bp mRNA), compared to variant 1, that cause a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform b) is much shorter than isoform a. Transcript variant 5 contains an additional segment (2475 bp mRNA), compared to variant 1, that causes a frameshift leading to an early stop codon. This transcript may function in a regulatory role with no protein translated. The predicted protein (isoform d) is much shorter than isoform a. |
| Pseudogene | There is an E2F6 pseudogene located on chromosome 22q11.2 (LOC376818) containing 2144 bp of the E2F6 gene with no introns. |
| |  |
| |
| | Diagram created by M. Oberley. |
| |
| Description | The predominately expressed isoform is 282 amino acids, and is . The DNA binding domain is thought to be between aa 50 and 129. It has a DEF box between aa 95 to 195. The dimerization domain is thought to reside between aa 130 and 222. There is a leucine zipper domain between aa 143 and 164. The transcriptional repression domain is located on the C terminus from aa 173 to 281. The N-terminal 1-75 aa are missing in isoform B which is predicted to be 206 AA. |
| Expression | Ubiquitous, though more highly expressed in the placenta, skeletal muscle, heart, ovary, kidney, small intestine and spleen. |
| Localisation | Nuclear |
| Function | Heterodimerization with DP1 or 2 creates a sequence specific transcriptional repressor. Overexpression of E2F6 can delay the exit of cells from S-phase, indicating a role for E2F6 in cell-cycle control. E2F6 has been shown via yeast two hybrid and co-IPs to interact with members of the polycomb repressive complex 1, such as Bmi1, RYBP, RING1, MEL-18, and Mph1. The functional outcome of these interactions are as of yet unclear. E2F6 has been biochemically purified in a complex containing polycomb group members h-1(3) mbt like protein, RING1, RING2, hMBLR, as well as YAF and HP1g; this complex also contained a novel euchromatic histone methyltransferase (Eu-HMTase1). This finding led to speculation that E2F6 controlled cellular entry into quiescence, but E2F6 nullizygous MEFs had no kinetic changes or defects in their ability to enter quiescence, or to re-enter into the cell-cycle. However, these animals had homeotic transformations of the axial skeleton, a phenotype that resembled Bmi1 nullizygous mice. This implicated E2F6 in regulation of normal development. |
| Homology | E2F6 has homology with E2Fs1-5 in the DNA-binding domain, the dimerization domain, and the marked box domain located between aa 231 and 239. |
| Dynamic recruitment of NF-Y and histone acetyltransferases on cell-cycle promoters. |
| Caretti G, Salsi V, Vecchi C, Imbriano C, Mantovani R |
| The Journal of biological chemistry. 2003 ; 278 (33) : 30435-30440. |
| PMID 12771133 |
| |
| E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription. |
| Cartwright P, Müller H, Wagener C, Holm K, Helin K |
| Oncogene. 1998 ; 17 (5) : 611-623. |
| PMID 9704927 |
| |
| Two different E2F6 proteins generated by alternative splicing and internal translation initiation. |
| Dahme T, Wood J, Livingston DM, Gaubatz S |
| European journal of biochemistry / FEBS. 2002 ; 269 (20) : 5030-5036. |
| PMID 12383262 |
| |
| Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6. |
| Gaubatz S, Wood JG, Livingston DM |
| Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (16) : 9190-9195. |
| PMID 9689056 |
| |
| Molecular cloning and characterization of the mouse E2F6 gene. |
| Kherrouche Z, Begue A, Stehelin D, Monté D |
| Biochemical and biophysical research communications. 2001 ; 288 (1) : 22-33. |
| PMID 11594747 |
| |
| An E2F-like repressor of transcription. |
| Morkel M, Wenkel J, Bannister AJ, Kouzarides T, Hagemeier C |
| Nature. 1997 ; 390 (6660) : 567-568. |
| PMID 9403682 |
| |
| E2F6 negatively regulates BRCA1 in human cancer cells without methylation of histone H3 on lysine 9. |
| Oberley MJ, Inman DR, Farnham PJ |
| The Journal of biological chemistry. 2003 ; 278 (43) : 42466-42476. |
| PMID 12909625 |
| |
| A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. |
| Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y |
| Science (New York, N.Y.). 2002 ; 296 (5570) : 1132-1136. |
| PMID 12004135 |
| |
| Homeotic transformations of the axial skeleton that accompany a targeted deletion of E2f6. |
| Storre J, Elsässer HP, Fuchs M, Ullmann D, Livingston DM, Gaubatz S |
| EMBO reports. 2002 ; 3 (7) : 695-700. |
| PMID 12101104 |
| |
| Sibling rivalry in the E2F family. |
| Trimarchi JM, Lees JA |
| Nature reviews. Molecular cell biology. 2002 ; 3 (1) : 11-20. |
| PMID 11823794 |
| |
| Nomenclature |
|---|
| HGNC (Hugo) | E2F6 3120 |
| Cards |
|---|
| Atlas | E2F6ID521 |
| Entrez_Gene (NCBI) | E2F6 1876 E2F transcription factor 6 |
| Aliases | E2F-6 |
| GeneCards (Weizmann) | E2F6 |
| Ensembl hg19 (Hinxton) | ENSG00000169016 [Gene_View] |
| Ensembl hg38 (Hinxton) | ENSG00000169016 [Gene_View] ENSG00000169016 [Sequence] chr2:11444375-11466177 [Contig_View] E2F6 [Vega] |
| ICGC DataPortal | ENSG00000169016 |
| TCGA cBioPortal | E2F6 |
| AceView (NCBI) | E2F6 |
| Genatlas (Paris) | E2F6 |
| WikiGenes | 1876 |
| SOURCE (Princeton) | E2F6 |
| Genetics Home Reference (NIH) | E2F6 |
| Genomic and cartography |
|---|
| GoldenPath hg38 (UCSC) | E2F6 - chr2:11444375-11466177 - 2p25.1 [Description] (hg38-Dec_2013) |
| GoldenPath hg19 (UCSC) | E2F6 - 2p25.1 [Description] (hg19-Feb_2009) |
| Ensembl | E2F6 - 2p25.1 [CytoView hg19] E2F6 - 2p25.1 [CytoView hg38] |
| Mapping of homologs : NCBI | E2F6 [Mapview hg19] E2F6 [Mapview hg38] |
| OMIM | 602944 |
| Gene and transcription |
|---|
| Genbank (Entrez) | AF041381 AF059292 AF088059 AK096197 AK223159 |
| RefSeq transcript (Entrez) | NM_001278275 NM_001278276 NM_001278277 NM_001278278 NM_198256 NM_198257 NM_198258 NM_198325 NM_212540 |
| RefSeq genomic (Entrez) | |
| Consensus coding sequences : CCDS (NCBI) | E2F6 |
| Cluster EST : Unigene | Hs.603093 [ NCBI ] |
| CGAP (NCI) | Hs.603093 |
| Alternative Splicing Gallery | ENSG00000169016 |
| Gene Expression | E2F6 [ NCBI-GEO ] E2F6 [ EBI - ARRAY_EXPRESS ]
E2F6 [ SEEK ] E2F6 [ MEM ] |
| Gene Expression Viewer (FireBrowse) | E2F6 [ Firebrowse - Broad ] |
| SOURCE (Princeton) | Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60] |
| Genevestigator | Expression in : [tissues] [cell-lines] [cancer] [perturbations] |
| BioGPS (Tissue expression) | 1876 |
| GTEX Portal (Tissue expression) | E2F6 |
| Human Protein Atlas | ENSG00000169016-E2F6 [pathology] [cell] [tissue] |
| Protein : pattern, domain, 3D structure |
|---|
| UniProt/SwissProt | O75461 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction] |
| NextProt | O75461 [Sequence] [Exons] [Medical] [Publications] |
| With graphics : InterPro | O75461 |
| Splice isoforms : SwissVar | O75461 |
| PhosPhoSitePlus | O75461 |
| Domains : Interpro (EBI) | E2F E2F-DP_heterodim E2F_CC-MB E2F_WHTH_DNA-bd_dom Transcription_factor_E2F6 WH-like_DNA-bd_sf WH_DNA-bd_sf |
| Domain families : Pfam (Sanger) | E2F_CC-MB (PF16421) E2F_TDP (PF02319) |
| Domain families : Pfam (NCBI) | pfam16421 pfam02319 |
| Domain families : Smart (EMBL) | E2F_TDP (SM01372) |
| Conserved Domain (NCBI) | E2F6 |
| DMDM Disease mutations | 1876 |
| Blocks (Seattle) | E2F6 |
| Superfamily | O75461 |
| Human Protein Atlas [tissue] | ENSG00000169016-E2F6 [tissue] |
| Peptide Atlas | O75461 |
| HPRD | 04251 |
| IPI | IPI00289560 IPI01011061 IPI00893548 IPI00414333 IPI00386595 IPI00893672 IPI00894414 |
| Protein Interaction databases |
|---|
| DIP (DOE-UCLA) | O75461 |
| IntAct (EBI) | O75461 |
| FunCoup | ENSG00000169016 |
| BioGRID | E2F6 |
| STRING (EMBL) | E2F6 |
| ZODIAC | E2F6 |
| Ontologies - Pathways |
|---|
| QuickGO | O75461 |
| Ontology : AmiGO | regulation of transcription involved in G1/S transition of mitotic cell cycle negative regulation of transcription by RNA polymerase II RNA polymerase II regulatory region sequence-specific DNA binding RNA polymerase II transcription factor activity, sequence-specific DNA binding RNA polymerase II transcription factor activity, sequence-specific DNA binding RNA polymerase II transcription factor activity, sequence-specific DNA binding transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA binding transcription corepressor activity protein binding nucleus nucleoplasm nucleoplasm transcription, DNA-templated protein dimerization activity negative regulation of G0 to G1 transition MLL1 complex RNA polymerase II transcription factor complex |
| Ontology : EGO-EBI | regulation of transcription involved in G1/S transition of mitotic cell cycle negative regulation of transcription by RNA polymerase II RNA polymerase II regulatory region sequence-specific DNA binding RNA polymerase II transcription factor activity, sequence-specific DNA binding RNA polymerase II transcription factor activity, sequence-specific DNA binding RNA polymerase II transcription factor activity, sequence-specific DNA binding transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA binding transcription corepressor activity protein binding nucleus nucleoplasm nucleoplasm transcription, DNA-templated protein dimerization activity negative regulation of G0 to G1 transition MLL1 complex RNA polymerase II transcription factor complex |
| REACTOME | O75461 [protein] |
| REACTOME Pathways | R-HSA-8953750 [pathway] |
| NDEx Network | E2F6 |
| Atlas of Cancer Signalling Network | E2F6 |
| Wikipedia pathways | E2F6 |
| Orthology - Evolution |
|---|
| OrthoDB | 1876 |
| GeneTree (enSembl) | ENSG00000169016 |
| Phylogenetic Trees/Animal Genes : TreeFam | E2F6 |
| HOVERGEN | O75461 |
| HOGENOM | O75461 |
| Homologs : HomoloGene | E2F6 |
| Homology/Alignments : Family Browser (UCSC) | E2F6 |
| Gene fusions - Rearrangements |
|---|
| Fusion : Mitelman | E2F6/LYRM4 [2p25.1/6p25.1] |
| Fusion : Mitelman | GREB1/E2F6 [2p25.1/2p25.1] [t(2;2)(p25;p25)] |
| Fusion Portal | E2F6 2p25.1 LYRM4 6p25.1 BRCA |
| Fusion : Quiver | E2F6 |
| Polymorphisms : SNP and Copy number variants |
|---|
| NCBI Variation Viewer | E2F6 [hg38] |
| dbSNP Single Nucleotide Polymorphism (NCBI) | E2F6 |
| dbVar | E2F6 |
| ClinVar | E2F6 |
| 1000_Genomes | E2F6 |
| Exome Variant Server | E2F6 |
| ExAC (Exome Aggregation Consortium) | ENSG00000169016 |
| GNOMAD Browser | ENSG00000169016 |
| Varsome Browser | E2F6 |
| Genetic variants : HAPMAP | 1876 |
| Genomic Variants (DGV) | E2F6 [DGVbeta] |
| DECIPHER | E2F6 [patients] [syndromes] [variants] [genes] |
| CONAN: Copy Number Analysis | E2F6 |
| Mutations |
|---|
| ICGC Data Portal | E2F6 |
| TCGA Data Portal | E2F6 |
| Broad Tumor Portal | E2F6 |
| OASIS Portal | E2F6 [ Somatic mutations - Copy number] |
| Somatic Mutations in Cancer : COSMIC | E2F6 [overview] [genome browser] [tissue] [distribution] |
| Mutations and Diseases : HGMD | E2F6 |
| LOVD (Leiden Open Variation Database) | Whole genome datasets |
| LOVD (Leiden Open Variation Database) | LOVD 3.0 shared installation |
| BioMuta | search E2F6 |
| DgiDB (Drug Gene Interaction Database) | E2F6 |
| DoCM (Curated mutations) | E2F6 (select the gene name) |
| CIViC (Clinical Interpretations of Variants in Cancer) | E2F6 (select a term) |
| intoGen | E2F6 |
| NCG5 (London) | E2F6 |
| Cancer3D | E2F6(select the gene name) |
| Impact of mutations | [PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser] |
| Diseases |
|---|
| OMIM | 602944 |
| Orphanet | |
| DisGeNET | E2F6 |
| Medgen | E2F6 |
| Genetic Testing Registry | E2F6
|
| NextProt | O75461 [Medical] |
| TSGene | 1876 |
| GENETests | E2F6 |
| Target Validation | E2F6 |
| Huge Navigator |
E2F6 [HugePedia] |
| snp3D : Map Gene to Disease | 1876 |
| BioCentury BCIQ | E2F6 |
| ClinGen | E2F6 |
| Clinical trials, drugs, therapy |
|---|
| Chemical/Protein Interactions : CTD | 1876 |
| Chemical/Pharm GKB Gene | PA27578 |
| Clinical trial | E2F6 |
| Miscellaneous |
|---|
| canSAR (ICR) | E2F6 (select the gene name) |
| Probes |
|---|
| Litterature |
|---|
| PubMed | 63 Pubmed reference(s) in Entrez |
| GeneRIFs | Gene References Into Functions (Entrez) |
| CoreMine | E2F6 |
| EVEX | E2F6 |
| GoPubMed | E2F6 |
| iHOP | E2F6 |
