Q58FA4 (E2F8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor E2F8
Short name=E2F-8

Gene names

Name:

E2f8

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	860 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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
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-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 process	Cell cycle Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Activator Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell 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 positive regulation of DNA endoreduplication Inferred from mutant phenotype Ref.7Ref.8. Source: UniProtKB sprouting angiogenesis Inferred from mutant phenotype Ref.5. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW trophoblast giant cell differentiation Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	nucleus Inferred from direct assay Ref.1. Source: MGI transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular_function	DNA binding Inferred from direct assay 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
itself		3	EBI-1390691,EBI-1390691

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 860	860	Transcription factor E2F8		PRO_0000298910
Regions
	DNA binding	113 – 182	70	Potential
	DNA binding	261 – 347	87	Potential
Experimental info
	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

Sequences

	Sequence		Length	Mass (Da)
	Q58FA4 [UniParc]. Last modified April 26, 2005. Version 1. Checksum: 792E3DDCA299ACE7	FASTA	860	93,276
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00553260.

RefSeq

NP_001013386.2. NM_001013368.5.

UniGene

Mm.240566.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WZH	model	-	A	263-341	[»]
			F	112-181	[»]

ProteinModelPortal

Q58FA4.

SMR

Q58FA4. Positions 112-180.

ModBase

Search...

PTM databases

PhosphoSite

Q58FA4.

Proteomic databases

PRIDE

Q58FA4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000058745; ENSMUSP00000056778; ENSMUSG00000046179.
ENSMUST00000119223; ENSMUSP00000112883; ENSMUSG00000046179.

GeneID

108961.

KEGG

mmu:108961.

UCSC

uc009haz.2. mouse.

Organism-specific databases

CTD

79733.

MGI

MGI:1922038. E2f8.

Phylogenomic databases

eggNOG

NOG320276.

GeneTree

ENSGT00530000063616.

HOGENOM

HOG000013193.

HOVERGEN

HBG063270.

InParanoid

Q58FA4.

KO

K09391.

OMA

LIPLTQC.

OrthoDB

EOG4V437R.

Gene expression databases

Bgee

Q58FA4.

CleanEx

MM_E2F8.

Genevestigator

Q58FA4.

Family and domain databases

Gene3D

1.10.10.10. 2 hits.

InterPro

IPR015633. E2F.
IPR003316. E2F_TDP.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

PANTHER

PTHR12081. PTHR12081. 1 hit.

Pfam

PF02319. E2F_TDP. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

E2F8. mouse.

NextBio

361528.

SOURCE

Search...

Entry information

Entry name

E2F8_MOUSE

Accession

Primary (citable) accession number: Q58FA4
Secondary accession number(s): Q3U4W2 , Q497V7, Q5PRE4, Q8BQJ5, Q8C3Y5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 21, 2007
Last sequence update:	April 26, 2005
Last modified:	May 1, 2013
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program