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Q58FA4

- E2F8_MOUSE

UniProt

Q58FA4 - E2F8_MOUSE

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Protein

Transcription factor E2F8

Gene
E2f8
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.5 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi113 – 18270 Reviewed predictionAdd
BLAST
DNA bindingi261 – 34787 Reviewed predictionAdd
BLAST

GO - Molecular functioni

  1. core promoter binding Source: Ensembl
  2. DNA binding Source: MGI
  3. identical protein binding Source: IntAct
  4. protein homodimerization activity Source: MGI
  5. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  6. transcription corepressor activity Source: UniProtKB

GO - Biological processi

  1. cell cycle comprising mitosis without cytokinesis Source: UniProtKB
  2. cell proliferation Source: MGI
  3. chorionic trophoblast cell differentiation Source: UniProtKB
  4. hepatocyte differentiation Source: UniProtKB
  5. negative regulation of cytokinesis Source: UniProtKB
  6. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  7. placenta development Source: UniProtKB
  8. positive regulation of DNA endoreduplication Source: UniProtKB
  9. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  10. sprouting angiogenesis Source: UniProtKB
  11. transcription, DNA-templated Source: UniProtKB-KW
  12. trophoblast giant cell differentiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Cell cycle, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor E2F8
Short name:
E2F-8
Gene namesi
Name:E2f8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1922038. E2f8.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. nucleus Source: MGI
  2. transcription factor complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi118 – 1192LG → EF: Loss of DNA-binding. 1 Publication
Mutagenesisi266 – 2672LR → EF: Loss of DNA-binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 860860Transcription factor E2F8PRO_0000298910Add
BLAST

Proteomic databases

PRIDEiQ58FA4.

PTM databases

PhosphoSiteiQ58FA4.

Expressioni

Tissue specificityi

Highly expressed in liver, skin, thymus and testis. Expressed in trophoblast giant cells throughout placenta development (at protein level).3 Publications

Inductioni

Induced at the onset of hepatocyte polyploidization.1 Publication

Gene expression databases

BgeeiQ58FA4.
CleanExiMM_E2F8.
GenevestigatoriQ58FA4.

Interactioni

Subunit structurei

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.

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-1390691,EBI-1390691

Protein-protein interaction databases

BioGridi224496. 1 interaction.
IntActiQ58FA4. 2 interactions.
MINTiMINT-8410110.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WZHmodel-A263-341[»]
F112-181[»]
ProteinModelPortaliQ58FA4.
SMRiQ58FA4. Positions 112-180.

Family & Domainsi

Domaini

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.

Sequence similaritiesi

Belongs to the E2F/DP family.

Phylogenomic databases

eggNOGiNOG320276.
GeneTreeiENSGT00530000063616.
HOGENOMiHOG000013193.
HOVERGENiHBG063270.
InParanoidiQ58FA4.
KOiK09391.
OMAiLIPLTQC.
OrthoDBiEOG7HHWSG.
PhylomeDBiQ58FA4.
TreeFamiTF105567.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR015633. E2F.
IPR003316. E2F_TDP.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR12081. PTHR12081. 1 hit.
PfamiPF02319. E2F_TDP. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q58FA4-1 [UniParc]FASTAAdd to Basket

« Hide

MENQKENLFS EPHKRGLMKS PLHPSSKANM VLAEIQPDLG PLTTPTKPKE    50
VSQGEPWTPT ANLKMLISAV SPEIRSRDQK RGLSDNRSAL PEARDCLHEH 100
LSGDEFEKSQ PSRKEKSLGL LCHKFLARYP KYPNPAVNND ICLDEVAEEL 150
NVERRRIYDI VNVLESLHMV SRLAKNRYTW HGRHNLTKTL GTLKSVGEEN 200
KYAEQIMMIK RKEYEQEFDF IKSCGIEDHV IKSHTGQNGH SDMCFVELPG 250
VEFRAASVNS RKDKSLRVMS QKFVMLFLVS TPQIVSLEIA AKILIGEDHV 300
EDLDKSKYKT KIRRLYDIAN VLSSLDLIKK VHVTEERGRK PAFKWTGPEI 350
SPNNSGSSPI MPLPASLEAE QSAKENCAKN LFSTRGKPSF TRHPSLIKLV 400
KSIENDRRKI SSAPSSPVKS NKAESSQNSP PVPNKMAQLA AICKMQLEEQ 450
SSEPRKKVKV NLARSGHYKP LAPLDPTVNT ELELLTPSLI QPLGVVPLIP 500
SPLSSAVPVI LPQAPSGPSY AIYLQPAQAQ MLTPPPGLSP TVCPTQPSNA 550
TGSKDPTDAP AEKTATDAAT TGSLQPAPER HGAKHRSKET TGDRGTKRMI 600
TAEDSGPSSV KKPKEDLKAL ENVPTPTPLF PSGYLIPLTQ CSSLGPDSVL 650
SNTENSGTPS PNHRIYGSPI AGVIPVASSE LTAVNFPPFH VTPLKLMVSP 700
TSMAAVPVGN SPALNSGHPA PAQNPSSAIV NFTLQHLGLI SPGVQMSASP 750
GPGAGTVPVS PRVEADNLSS RQRRATNHDS PVLGQSQLNG QPVAGTGAQQ 800
PVPVTPKGSQ LVAENFFRTP GGPTKPTSSP YTDFDGANKT SFGTLFVPQR 850
KLEVSTEDIH 860
Length:860
Mass (Da):93,276
Last modified:April 26, 2005 - v1
Checksum:i792E3DDCA299ACE7
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti65 – 651M → T in BAC33794. 1 Publication
Sequence conflicti138 – 1381N → Y in AAH86675. 1 Publication
Sequence conflicti155 – 1551R → Q in BAC39205. 1 Publication
Sequence conflicti209 – 2091I → T in BAC39205. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS39967.1.
RefSeqiNP_001013386.2. NM_001013368.5.
XP_006540616.1. XM_006540553.1.
XP_006540617.1. XM_006540554.1.
UniGeneiMm.240566.

Genome annotation databases

EnsembliENSMUST00000058745; ENSMUSP00000056778; ENSMUSG00000046179.
ENSMUST00000119223; ENSMUSP00000112883; ENSMUSG00000046179.
GeneIDi108961.
KEGGimmu:108961.
UCSCiuc009haz.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS39967.1.
RefSeqi NP_001013386.2. NM_001013368.5.
XP_006540616.1. XM_006540553.1.
XP_006540617.1. XM_006540554.1.
UniGenei Mm.240566.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1WZH model - A 263-341 [» ]
F 112-181 [» ]
ProteinModelPortali Q58FA4.
SMRi Q58FA4. Positions 112-180.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 224496. 1 interaction.
IntActi Q58FA4. 2 interactions.
MINTi MINT-8410110.

PTM databases

PhosphoSitei Q58FA4.

Proteomic databases

PRIDEi Q58FA4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000058745 ; ENSMUSP00000056778 ; ENSMUSG00000046179 .
ENSMUST00000119223 ; ENSMUSP00000112883 ; ENSMUSG00000046179 .
GeneIDi 108961.
KEGGi mmu:108961.
UCSCi uc009haz.2. mouse.

Organism-specific databases

CTDi 79733.
MGIi MGI:1922038. E2f8.

Phylogenomic databases

eggNOGi NOG320276.
GeneTreei ENSGT00530000063616.
HOGENOMi HOG000013193.
HOVERGENi HBG063270.
InParanoidi Q58FA4.
KOi K09391.
OMAi LIPLTQC.
OrthoDBi EOG7HHWSG.
PhylomeDBi Q58FA4.
TreeFami TF105567.

Miscellaneous databases

ChiTaRSi E2F8. mouse.
NextBioi 361528.
PROi Q58FA4.
SOURCEi Search...

Gene expression databases

Bgeei Q58FA4.
CleanExi MM_E2F8.
Genevestigatori Q58FA4.

Family and domain databases

Gene3Di 1.10.10.10. 2 hits.
InterProi IPR015633. E2F.
IPR003316. E2F_TDP.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view ]
PANTHERi PTHR12081. PTHR12081. 1 hit.
Pfami PF02319. E2F_TDP. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: FUNCTION, TISSUE SPECIFICITY.
  7. Cited for: FUNCTION, INDUCTION.
  8. Cited for: FUNCTION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiE2F8_MOUSE
AccessioniPrimary (citable) accession number: Q58FA4
Secondary accession number(s): Q3U4W2
, Q497V7, Q5PRE4, Q8BQJ5, Q8C3Y5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 21, 2007
Last sequence update: April 26, 2005
Last modified: July 9, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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