ID   E2F8_MOUSE              Reviewed;         860 AA.
AC   Q58FA4; Q3U4W2; Q497V7; Q5PRE4; Q8BQJ5; Q8C3Y5;
DT   21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2005, sequence version 1.
DT   09-DEC-2015, entry version 113.
DE   RecName: Full=Transcription factor E2F8;
DE            Short=E2F-8;
GN   Name=E2f8;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   SELF-ASSOCIATION, AND MUTAGENESIS OF 118-LEU-GLY-119 AND
RP   266-LEU-ARG-267.
RC   STRAIN=Swiss Webster;
RX   PubMed=15722552; DOI=10.1074/jbc.M501410200;
RA   Maiti B., Li J., de Bruin A., Gordon F., Timmers C., Opavsky R.,
RA   Patil K., Tuttle J., Cleghorn W., Leone G.;
RT   "Cloning and characterization of mouse E2F8, a novel mammalian E2F
RT   family member capable of blocking cellular proliferation.";
RL   J. Biol. Chem. 280:18211-18220(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Heart, Liver, Spleen, and Thymus;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Head, and Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18194653; DOI=10.1016/j.devcel.2007.10.017;
RA   Li J., Ran C., Li E., Gordon F., Comstock G., Siddiqui H.,
RA   Cleghorn W., Chen H.-Z., Kornacker K., Liu C.-G., Pandit S.K.,
RA   Khanizadeh M., Weinstein M., Leone G., de Bruin A.;
RT   "Synergistic function of E2F7 and E2F8 is essential for cell survival
RT   and embryonic development.";
RL   Dev. Cell 14:62-75(2008).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   FUNCTION.
RX   PubMed=22903062; DOI=10.1038/emboj.2012.231;
RA   Weijts B.G., Bakker W.J., Cornelissen P.W., Liang K.H.,
RA   Schaftenaar F.H., Westendorp B., de Wolf C.A., Paciejewska M.,
RA   Scheele C.L., Kent L., Leone G., Schulte-Merker S., de Bruin A.;
RT   "E2F7 and E2F8 promote angiogenesis through transcriptional activation
RT   of VEGFA in cooperation with HIF1.";
RL   EMBO J. 31:3871-3884(2012).
RN   [7]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=22516201; DOI=10.1016/j.devcel.2012.01.013;
RA   Ouseph M.M., Li J., Chen H.Z., Pecot T., Wenzel P., Thompson J.C.,
RA   Comstock G., Chokshi V., Byrne M., Forde B., Chong J.L., Huang K.,
RA   Machiraju R., de Bruin A., Leone G.;
RT   "Atypical E2F repressors and activators coordinate placental
RT   development.";
RL   Dev. Cell 22:849-862(2012).
RN   [8]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=23064264; DOI=10.1038/ncb2585;
RA   Pandit S.K., Westendorp B., Nantasanti S., van Liere E., Tooten P.C.,
RA   Cornelissen P.W., Toussaint M.J., Lamers W.H., de Bruin A.;
RT   "E2F8 is essential for polyploidization in mammalian cells.";
RL   Nat. Cell Biol. 14:1181-1191(2012).
RN   [9]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=23064266; DOI=10.1038/ncb2595;
RA   Chen H.Z., Ouseph M.M., Li J., Pecot T., Chokshi V., Kent L., Bae S.,
RA   Byrne M., Duran C., Comstock G., Trikha P., Mair M., Senapati S.,
RA   Martin C.K., Gandhi S., Wilson N., Liu B., Huang Y.W., Thompson J.C.,
RA   Raman S., Singh S., Leone M., Machiraju R., Huang K., Mo X.,
RA   Fernandez S., Kalaszczynska I., Wolgemuth D.J., Sicinski P., Huang T.,
RA   Jin V., Leone G.;
RT   "Canonical and atypical E2Fs regulate the mammalian endocycle.";
RL   Nat. Cell Biol. 14:1192-1202(2012).
CC   -!- FUNCTION: Atypical E2F transcription factor that participates in
CC       various processes such as angiogenesis and polyploidization of
CC       specialized cells. Mainly acts as a transcription repressor that
CC       binds DNA independently of DP proteins and specifically recognizes
CC       the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses
CC       transcription of classical E2F transcription factors such as E2F1:
CC       component of a feedback loop in S phase by repressing the
CC       expression of E2F1, thereby preventing p53/TP53-dependent
CC       apoptosis. Plays a key role in polyploidization of cells in
CC       placenta and liver by regulating the endocycle, probably by
CC       repressing genes promoting cytokinesis and antagonizing action of
CC       classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for
CC       placental development by promoting polyploidization of trophoblast
CC       giant cells. Acts as a promoter of sprouting angiogenesis,
CC       possibly by acting as a transcription activator: associates with
CC       HIF1A, recognizes and binds the VEGFA promoter, which is different
CC       from canonical E2 recognition site, and activates expression of
CC       the VEGFA gene. {ECO:0000269|PubMed:18194653,
CC       ECO:0000269|PubMed:22516201, ECO:0000269|PubMed:22903062,
CC       ECO:0000269|PubMed:23064264, ECO:0000269|PubMed:23064266}.
CC   -!- SUBUNIT: Interacts with HIF1A (By similarity). Homodimer and
CC       heterodimer: mainly forms homodimers and, to a lesser extent,
CC       heterodimers with E2F8. Dimerization is important for DNA-binding.
CC       {ECO:0000250}.
CC   -!- INTERACTION:
CC       Self; NbExp=3; IntAct=EBI-1390691, EBI-1390691;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15722552}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in liver, skin, thymus and
CC       testis. Expressed in trophoblast giant cells throughout placenta
CC       development (at protein level). {ECO:0000269|PubMed:15722552,
CC       ECO:0000269|PubMed:22516201, ECO:0000269|PubMed:23064266}.
CC   -!- INDUCTION: Induced at the onset of hepatocyte polyploidization.
CC       {ECO:0000269|PubMed:23064264}.
CC   -!- DOMAIN: In contrast to classical members of the E2F transcription
CC       factor, atypical members contain 2 DNA-binding domains and
CC       regulate transcription in a DP-independent manner. Both DNA-
CC       binding domains are required for DNA-binding and are proposed to
CC       form an intramolecular structure that is similar to the winged
CC       helix structure of the E2F-DP heterodimer (By similarity).
CC       {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: No visible phenotype; mice develop normally
CC       and live to old age. E2f7 and E2f8 double knockout embryos die by
CC       11.5 dpc of massive apoptosis and dilation of blood vessels and
CC       show increased expression of E2f1 and p53/Tp53, as well as many
CC       stress-related genes. {ECO:0000269|PubMed:18194653}.
CC   -!- SIMILARITY: Belongs to the E2F/DP family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AY957576; AAX49603.1; -; mRNA.
DR   EMBL; AK049525; BAC33794.1; -; mRNA.
DR   EMBL; AK084513; BAC39205.1; -; mRNA.
DR   EMBL; AK154018; BAE32318.1; -; mRNA.
DR   EMBL; AK157235; BAE34010.1; -; mRNA.
DR   EMBL; AK160240; BAE35708.1; -; mRNA.
DR   EMBL; BC086675; AAH86675.1; -; mRNA.
DR   EMBL; BC100357; AAI00358.1; -; mRNA.
DR   CCDS; CCDS39967.1; -.
DR   RefSeq; NP_001013386.2; NM_001013368.5.
DR   RefSeq; XP_006540616.1; XM_006540553.2.
DR   RefSeq; XP_006540617.1; XM_006540554.2.
DR   UniGene; Mm.240566; -.
DR   PDB; 1WZH; Model; -; A=263-341, F=112-181.
DR   PDBsum; 1WZH; -.
DR   ProteinModelPortal; Q58FA4; -.
DR   SMR; Q58FA4; 112-180.
DR   BioGrid; 224496; 1.
DR   IntAct; Q58FA4; 2.
DR   MINT; MINT-8410110; -.
DR   STRING; 10090.ENSMUSP00000056778; -.
DR   PhosphoSite; Q58FA4; -.
DR   PaxDb; Q58FA4; -.
DR   PRIDE; Q58FA4; -.
DR   Ensembl; ENSMUST00000058745; ENSMUSP00000056778; ENSMUSG00000046179.
DR   Ensembl; ENSMUST00000119223; ENSMUSP00000112883; ENSMUSG00000046179.
DR   GeneID; 108961; -.
DR   KEGG; mmu:108961; -.
DR   UCSC; uc009haz.2; mouse.
DR   CTD; 79733; -.
DR   MGI; MGI:1922038; E2f8.
DR   eggNOG; KOG2578; Eukaryota.
DR   eggNOG; ENOG4111IGY; LUCA.
DR   GeneTree; ENSGT00530000063616; -.
DR   HOGENOM; HOG000013193; -.
DR   HOVERGEN; HBG063270; -.
DR   InParanoid; Q58FA4; -.
DR   KO; K09391; -.
DR   OMA; LIPLTQC; -.
DR   OrthoDB; EOG7HHWSG; -.
DR   PhylomeDB; Q58FA4; -.
DR   TreeFam; TF105567; -.
DR   ChiTaRS; E2f8; mouse.
DR   NextBio; 361528; -.
DR   PRO; PR:Q58FA4; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   Bgee; Q58FA4; -.
DR   CleanEx; MM_E2F8; -.
DR   Genevisible; Q58FA4; MM.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0005667; C:transcription factor complex; IEA:InterPro.
DR   GO; GO:0001047; F:core promoter binding; ISO:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:MGI.
DR   GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:0003714; F:transcription corepressor activity; IMP:UniProtKB.
DR   GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IMP:UniProtKB.
DR   GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; ISO:MGI.
DR   GO; GO:0033301; P:cell cycle comprising mitosis without cytokinesis; IMP:UniProtKB.
DR   GO; GO:0008283; P:cell proliferation; IDA:MGI.
DR   GO; GO:0060718; P:chorionic trophoblast cell differentiation; IMP:UniProtKB.
DR   GO; GO:0070365; P:hepatocyte differentiation; IMP:UniProtKB.
DR   GO; GO:0032466; P:negative regulation of cytokinesis; IMP:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
DR   GO; GO:0001890; P:placenta development; IMP:UniProtKB.
DR   GO; GO:0032877; P:positive regulation of DNA endoreduplication; IMP:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISO:MGI.
DR   GO; GO:0002040; P:sprouting angiogenesis; IMP:UniProtKB.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR   GO; GO:0060707; P:trophoblast giant cell differentiation; IMP:UniProtKB.
DR   Gene3D; 1.10.10.10; -; 2.
DR   InterPro; IPR015633; E2F.
DR   InterPro; IPR003316; E2F_WHTH_DNA-bd_dom.
DR   InterPro; IPR011991; WHTH_DNA-bd_dom.
DR   PANTHER; PTHR12081; PTHR12081; 5.
DR   Pfam; PF02319; E2F_TDP; 2.
DR   SUPFAM; SSF46785; SSF46785; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Cell cycle; Complete proteome; DNA-binding;
KW   Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW   Transcription regulation.
FT   CHAIN         1    860       Transcription factor E2F8.
FT                                /FTId=PRO_0000298910.
FT   DNA_BIND    113    182       {ECO:0000255}.
FT   DNA_BIND    261    347       {ECO:0000255}.
FT   MOD_RES      71     71       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MUTAGEN     118    119       LG->EF: Loss of DNA-binding.
FT                                {ECO:0000269|PubMed:15722552}.
FT   MUTAGEN     266    267       LR->EF: Loss of DNA-binding.
FT                                {ECO:0000269|PubMed:15722552}.
FT   CONFLICT     65     65       M -> T (in Ref. 2; BAC33794).
FT                                {ECO:0000305}.
FT   CONFLICT    138    138       N -> Y (in Ref. 3; AAH86675).
FT                                {ECO:0000305}.
FT   CONFLICT    155    155       R -> Q (in Ref. 2; BAC39205).
FT                                {ECO:0000305}.
FT   CONFLICT    209    209       I -> T (in Ref. 2; BAC39205).
FT                                {ECO:0000305}.
SQ   SEQUENCE   860 AA;  93276 MW;  792E3DDCA299ACE7 CRC64;
     MENQKENLFS EPHKRGLMKS PLHPSSKANM VLAEIQPDLG PLTTPTKPKE VSQGEPWTPT
     ANLKMLISAV SPEIRSRDQK RGLSDNRSAL PEARDCLHEH LSGDEFEKSQ PSRKEKSLGL
     LCHKFLARYP KYPNPAVNND ICLDEVAEEL NVERRRIYDI VNVLESLHMV SRLAKNRYTW
     HGRHNLTKTL GTLKSVGEEN KYAEQIMMIK RKEYEQEFDF IKSCGIEDHV IKSHTGQNGH
     SDMCFVELPG VEFRAASVNS RKDKSLRVMS QKFVMLFLVS TPQIVSLEIA AKILIGEDHV
     EDLDKSKYKT KIRRLYDIAN VLSSLDLIKK VHVTEERGRK PAFKWTGPEI SPNNSGSSPI
     MPLPASLEAE QSAKENCAKN LFSTRGKPSF TRHPSLIKLV KSIENDRRKI SSAPSSPVKS
     NKAESSQNSP PVPNKMAQLA AICKMQLEEQ SSEPRKKVKV NLARSGHYKP LAPLDPTVNT
     ELELLTPSLI QPLGVVPLIP SPLSSAVPVI LPQAPSGPSY AIYLQPAQAQ MLTPPPGLSP
     TVCPTQPSNA TGSKDPTDAP AEKTATDAAT TGSLQPAPER HGAKHRSKET TGDRGTKRMI
     TAEDSGPSSV KKPKEDLKAL ENVPTPTPLF PSGYLIPLTQ CSSLGPDSVL SNTENSGTPS
     PNHRIYGSPI AGVIPVASSE LTAVNFPPFH VTPLKLMVSP TSMAAVPVGN SPALNSGHPA
     PAQNPSSAIV NFTLQHLGLI SPGVQMSASP GPGAGTVPVS PRVEADNLSS RQRRATNHDS
     PVLGQSQLNG QPVAGTGAQQ PVPVTPKGSQ LVAENFFRTP GGPTKPTSSP YTDFDGANKT
     SFGTLFVPQR KLEVSTEDIH
//