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Q58FA4 (E2F8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcription factor E2F8

Short name=E2F-8
Gene names
Name:E2f8
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length860 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Atypical E2F transcription factor that participates in 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

Subunit structure

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.

Subcellular location

Nucleus Ref.1.

Tissue specificity

Highly expressed in liver, skin, thymus and testis. Expressed in trophoblast giant cells throughout placenta development (at protein level). Ref.1 Ref.6 Ref.8

Induction

Induced at the onset of hepatocyte polyploidization. Ref.7

Domain

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.

Disruption phenotype

No visible phenotype; mice develop normally and live to old age. E2f7 and 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

Sequence similarities

Belongs to the E2F/DP family.

Ontologies

Keywords
   Biological processCell cycle
Transcription
Transcription regulation
   Cellular componentNucleus
   LigandDNA-binding
   Molecular functionActivator
Repressor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle comprising mitosis without cytokinesis

Inferred from mutant phenotype Ref.8. Source: UniProtKB

cell proliferation

Inferred from direct assay Ref.1. Source: MGI

chorionic trophoblast cell differentiation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

hepatocyte differentiation

Inferred from mutant phenotype Ref.7Ref.8. Source: UniProtKB

negative regulation of cytokinesis

Inferred from mutant phenotype Ref.7Ref.8. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype Ref.6Ref.7Ref.8. Source: UniProtKB

placenta development

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of DNA endoreduplication

Inferred from mutant phenotype Ref.7Ref.8. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

sprouting angiogenesis

Inferred from mutant phenotype Ref.5. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

trophoblast giant cell differentiation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

   Cellular_componentnucleus

Inferred from direct assay Ref.1. Source: MGI

transcription factor complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionDNA binding

Inferred from direct assay Ref.1. Source: MGI

core promoter binding

Inferred from electronic annotation. Source: Ensembl

identical protein binding

Inferred from physical interaction Ref.1. Source: IntAct

protein homodimerization activity

Inferred from physical interaction Ref.1. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype Ref.6Ref.7Ref.8. Source: UniProtKB

transcription corepressor activity

Inferred from mutant phenotype Ref.6Ref.7Ref.8. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself3EBI-1390691,EBI-1390691

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 860860Transcription factor E2F8
PRO_0000298910

Regions

DNA binding113 – 18270 Potential
DNA binding261 – 34787 Potential

Experimental info

Mutagenesis118 – 1192LG → EF: Loss of DNA-binding. Ref.1
Mutagenesis266 – 2672LR → EF: Loss of DNA-binding. Ref.1
Sequence conflict651M → T in BAC33794. Ref.2
Sequence conflict1381N → Y in AAH86675. Ref.3
Sequence conflict1551R → Q in BAC39205. Ref.2
Sequence conflict2091I → T in BAC39205. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q58FA4 [UniParc].

Last modified April 26, 2005. Version 1.
Checksum: 792E3DDCA299ACE7

FASTA86093,276
        10         20         30         40         50         60 
MENQKENLFS EPHKRGLMKS PLHPSSKANM VLAEIQPDLG PLTTPTKPKE VSQGEPWTPT 

        70         80         90        100        110        120 
ANLKMLISAV SPEIRSRDQK RGLSDNRSAL PEARDCLHEH LSGDEFEKSQ PSRKEKSLGL 

       130        140        150        160        170        180 
LCHKFLARYP KYPNPAVNND ICLDEVAEEL NVERRRIYDI VNVLESLHMV SRLAKNRYTW 

       190        200        210        220        230        240 
HGRHNLTKTL GTLKSVGEEN KYAEQIMMIK RKEYEQEFDF IKSCGIEDHV IKSHTGQNGH 

       250        260        270        280        290        300 
SDMCFVELPG VEFRAASVNS RKDKSLRVMS QKFVMLFLVS TPQIVSLEIA AKILIGEDHV 

       310        320        330        340        350        360 
EDLDKSKYKT KIRRLYDIAN VLSSLDLIKK VHVTEERGRK PAFKWTGPEI SPNNSGSSPI 

       370        380        390        400        410        420 
MPLPASLEAE QSAKENCAKN LFSTRGKPSF TRHPSLIKLV KSIENDRRKI SSAPSSPVKS 

       430        440        450        460        470        480 
NKAESSQNSP PVPNKMAQLA AICKMQLEEQ SSEPRKKVKV NLARSGHYKP LAPLDPTVNT 

       490        500        510        520        530        540 
ELELLTPSLI QPLGVVPLIP SPLSSAVPVI LPQAPSGPSY AIYLQPAQAQ MLTPPPGLSP 

       550        560        570        580        590        600 
TVCPTQPSNA TGSKDPTDAP AEKTATDAAT TGSLQPAPER HGAKHRSKET TGDRGTKRMI 

       610        620        630        640        650        660 
TAEDSGPSSV KKPKEDLKAL ENVPTPTPLF PSGYLIPLTQ CSSLGPDSVL SNTENSGTPS 

       670        680        690        700        710        720 
PNHRIYGSPI AGVIPVASSE LTAVNFPPFH VTPLKLMVSP TSMAAVPVGN SPALNSGHPA 

       730        740        750        760        770        780 
PAQNPSSAIV NFTLQHLGLI SPGVQMSASP GPGAGTVPVS PRVEADNLSS RQRRATNHDS 

       790        800        810        820        830        840 
PVLGQSQLNG QPVAGTGAQQ PVPVTPKGSQ LVAENFFRTP GGPTKPTSSP YTDFDGANKT 

       850        860 
SFGTLFVPQR KLEVSTEDIH 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferation."
Maiti B., Li J., de Bruin A., Gordon F., Timmers C., Opavsky R., Patil K., Tuttle J., Cleghorn W., Leone G.
J. Biol. Chem. 280:18211-18220(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, SELF-ASSOCIATION, MUTAGENESIS OF 118-LEU-GLY-119 AND 266-LEU-ARG-267.
Strain: Swiss Webster.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Heart, Liver, Spleen and Thymus.
[3]"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].
Strain: C57BL/6.
Tissue: Head and Placenta.
[4]"Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development."
Li J., Ran C., Li E., Gordon F., Comstock G., Siddiqui H., Cleghorn W., Chen H.-Z., Kornacker K., Liu C.-G., Pandit S.K., Khanizadeh M., Weinstein M., Leone G., de Bruin A.
Dev. Cell 14:62-75(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[5]"E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1."
Weijts B.G., Bakker W.J., Cornelissen P.W., Liang K.H., Schaftenaar F.H., Westendorp B., de Wolf C.A., Paciejewska M., Scheele C.L., Kent L., Leone G., Schulte-Merker S., de Bruin A.
EMBO J. 31:3871-3884(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Atypical E2F repressors and activators coordinate placental development."
Ouseph M.M., Li J., Chen H.Z., Pecot T., Wenzel P., Thompson J.C., Comstock G., Chokshi V., Byrne M., Forde B., Chong J.L., Huang K., Machiraju R., de Bruin A., Leone G.
Dev. Cell 22:849-862(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[7]"E2F8 is essential for polyploidization in mammalian cells."
Pandit S.K., Westendorp B., Nantasanti S., van Liere E., Tooten P.C., Cornelissen P.W., Toussaint M.J., Lamers W.H., de Bruin A.
Nat. Cell Biol. 14:1181-1191(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[8]"Canonical and atypical E2Fs regulate the mammalian endocycle."
Chen H.Z., Ouseph M.M., Li J., Pecot T., Chokshi V., Kent L., Bae S., Byrne M., Duran C., Comstock G., Trikha P., Mair M., Senapati S., Martin C.K., Gandhi S., Wilson N., Liu B., Huang Y.W. expand/collapse author list , Thompson J.C., Raman S., Singh S., Leone M., Machiraju R., Huang K., Mo X., Fernandez S., Kalaszczynska I., Wolgemuth D.J., Sicinski P., Huang T., Jin V., Leone G.
Nat. Cell Biol. 14:1192-1202(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001013386.2. NM_001013368.5.
XP_006540616.1. XM_006540553.1.
XP_006540617.1. XM_006540554.1.
UniGeneMm.240566.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WZHmodel-A263-341[»]
F112-181[»]
ProteinModelPortalQ58FA4.
SMRQ58FA4. Positions 112-183, 260-345.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid224496. 1 interaction.
IntActQ58FA4. 2 interactions.
MINTMINT-8410110.

PTM databases

PhosphoSiteQ58FA4.

Proteomic databases

PRIDEQ58FA4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000058745; ENSMUSP00000056778; ENSMUSG00000046179.
ENSMUST00000119223; ENSMUSP00000112883; ENSMUSG00000046179.
GeneID108961.
KEGGmmu:108961.
UCSCuc009haz.2. mouse.

Organism-specific databases

CTD79733.
MGIMGI:1922038. E2f8.

Phylogenomic databases

eggNOGNOG320276.
GeneTreeENSGT00530000063616.
HOGENOMHOG000013193.
HOVERGENHBG063270.
InParanoidQ58FA4.
KOK09391.
OMALIPLTQC.
OrthoDBEOG7HHWSG.
PhylomeDBQ58FA4.
TreeFamTF105567.

Gene expression databases

BgeeQ58FA4.
CleanExMM_E2F8.
GenevestigatorQ58FA4.

Family and domain databases

Gene3D1.10.10.10. 2 hits.
InterProIPR015633. E2F.
IPR003316. E2F_TDP.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERPTHR12081. PTHR12081. 1 hit.
PfamPF02319. E2F_TDP. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSE2F8. mouse.
NextBio361528.
PROQ58FA4.
SOURCESearch...

Entry information

Entry nameE2F8_MOUSE
AccessionPrimary (citable) accession number: Q58FA4
Secondary accession number(s): Q3U4W2 expand/collapse secondary AC list , Q497V7, Q5PRE4, Q8BQJ5, Q8C3Y5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 21, 2007
Last sequence update: April 26, 2005
Last modified: April 16, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot