Q58FA4 (E2F8_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 88. History...
Names and origin
|Protein names||Recommended name:|
Transcription factor E2F8
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||860 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Atypical E2F transcription factor that participates to various processes such as angiogenesis and polyploidization of specialized cells. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Interacts with HIF1A By similarity. Homodimer and heterodimer: mainly forms homodimers and, to a lesser extent, heterodimers with E2F8. Dimerization is important for DNA-binding.
Induced at the onset of hepatocyte polyploidization. Ref.7
In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer By similarity.
No visible phenotype; mice develop normally and live to old age. E2f7-E2f8 double-knockout embryos die by 11.5 dpc of massive apoptosis and dilation of blood vessels and show increased expression of E2f1 and p53/Tp53, as well as many stress-related genes. Ref.4
Belongs to the E2F/DP family.
|Biological process||Cell cycle|
|Gene Ontology (GO)|
|Biological_process||cell cycle comprising mitosis without cytokinesiscell proliferationchorionic trophoblast cell differentiationhepatocyte differentiationnegative regulation of cytokinesisnegative regulation of transcription from RNA polymerase II promoterpositive regulation of DNA endoreduplicationsprouting angiogenesistranscription, DNA-dependent|
Inferred from electronic annotation. Source: UniProtKB-KWtrophoblast giant cell differentiation
|Cellular_component||nucleustranscription factor complex|
Inferred from electronic annotation. Source: InterPro
|Molecular_function||DNA bindingsequence-specific DNA binding transcription factor activitytranscription corepressor activity|
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 860||860||Transcription factor E2F8||PRO_0000298910|
|DNA binding||113 – 182||70||Potential|
|DNA binding||261 – 347||87||Potential|
|Mutagenesis||118 – 119||2||LG → EF: Loss of DNA-binding. Ref.1|
|Mutagenesis||266 – 267||2||LR → EF: Loss of DNA-binding. Ref.1|
|Sequence conflict||65||1||M → T in BAC33794. Ref.2|
|Sequence conflict||138||1||N → Y in AAH86675. Ref.3|
|Sequence conflict||155||1||R → Q in BAC39205. Ref.2|
|Sequence conflict||209||1||I → T in BAC39205. Ref.2|
|AY957576 mRNA. Translation: AAX49603.1.|
AK049525 mRNA. Translation: BAC33794.1.
AK084513 mRNA. Translation: BAC39205.1.
AK154018 mRNA. Translation: BAE32318.1.
AK157235 mRNA. Translation: BAE34010.1.
AK160240 mRNA. Translation: BAE35708.1.
BC086675 mRNA. Translation: AAH86675.1.
BC100357 mRNA. Translation: AAI00358.1.
|RefSeq||NP_001013386.2. NM_001013368.5. |
3D structure databases
|SMR||Q58FA4. Positions 112-180. |
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000058745; ENSMUSP00000056778; ENSMUSG00000046179. |
ENSMUST00000119223; ENSMUSP00000112883; ENSMUSG00000046179.
|UCSC||uc009haz.2. mouse. |
|MGI||MGI:1922038. E2f8. |
Gene expression databases
Family and domain databases
|Gene3D||188.8.131.52. 2 hits. |
|InterPro||IPR015633. E2F. |
|PANTHER||PTHR12081. PTHR12081. 1 hit. |
|Pfam||PF02319. E2F_TDP. 2 hits. |
|ChiTaRS||E2F8. mouse. |
|Accession||Primary (citable) accession number: Q58FA4|
Secondary accession number(s): Q3U4W2 Q8C3Y5
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|