E2F8_MOUSE
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 03-AUG-2022, entry version 152.
DE RecName: Full=Transcription factor E2F8;
DE Short=E2F-8;
GN Name=E2f8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC 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 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., Patil K.,
RA Tuttle J., Cleghorn W., Leone G.;
RT "Cloning and characterization of mouse E2F8, a novel mammalian E2F family
RT 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., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., 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., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., 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 project:
RT 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., Cleghorn W.,
RA Chen H.-Z., Kornacker K., Liu C.-G., Pandit S.K., Khanizadeh M.,
RA Weinstein M., Leone G., de Bruin A.;
RT "Synergistic function of E2F7 and E2F8 is essential for cell survival and
RT embryonic development.";
RL Dev. Cell 14:62-75(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION BY
RP 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 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., Schaftenaar F.H.,
RA Westendorp B., de Wolf C.A., Paciejewska M., Scheele C.L., Kent L.,
RA Leone G., Schulte-Merker S., de Bruin A.;
RT "E2F7 and E2F8 promote angiogenesis through transcriptional activation of
RT 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 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., Fernandez S.,
RA Kalaszczynska I., Wolgemuth D.J., Sicinski P., Huang T., 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 binds
CC DNA independently of DP proteins and specifically recognizes the E2
CC recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of
CC classical E2F transcription factors such as E2F1: component of a
CC feedback loop in S phase by repressing the expression of E2F1, thereby
CC preventing p53/TP53-dependent apoptosis. Plays a key role in
CC polyploidization of cells in placenta and liver by regulating the
CC endocycle, probably by repressing genes promoting cytokinesis and
CC antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3).
CC Required for placental development by promoting polyploidization of
CC trophoblast giant cells. Acts as a promoter of sprouting angiogenesis,
CC possibly by acting as a transcription activator: associates with HIF1A,
CC recognizes and binds the VEGFA promoter, which is different from
CC canonical E2 recognition site, and activates expression of the VEGFA
CC gene. {ECO:0000269|PubMed:18194653, ECO:0000269|PubMed:22516201,
CC ECO:0000269|PubMed:22903062, ECO:0000269|PubMed:23064264,
CC 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 Q58FA4; Q58FA4: E2f8; 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 testis.
CC Expressed in trophoblast giant cells throughout placenta development
CC (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 regulate
CC transcription in a DP-independent manner. Both DNA-binding domains are
CC required for DNA-binding and are proposed to form an intramolecular
CC structure that is similar to the winged helix structure of the E2F-DP
CC heterodimer (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype; mice develop normally and
CC live to old age. E2f7 and E2f8 double knockout embryos die by 11.5 dpc
CC of massive apoptosis and dilation of blood vessels and show increased
CC expression of E2f1 and p53/Tp53, as well as many stress-related genes.
CC {ECO:0000269|PubMed:18194653}.
CC -!- SIMILARITY: Belongs to the E2F/DP family. {ECO:0000305}.
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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_006540553.3.
DR RefSeq; XP_006540617.1; XM_006540554.3.
DR AlphaFoldDB; Q58FA4; -.
DR SMR; Q58FA4; -.
DR BioGRID; 224496; 1.
DR IntAct; Q58FA4; 2.
DR MINT; Q58FA4; -.
DR STRING; 10090.ENSMUSP00000056778; -.
DR iPTMnet; Q58FA4; -.
DR PhosphoSitePlus; Q58FA4; -.
DR EPD; Q58FA4; -.
DR jPOST; Q58FA4; -.
DR MaxQB; Q58FA4; -.
DR PaxDb; Q58FA4; -.
DR PeptideAtlas; Q58FA4; -.
DR PRIDE; Q58FA4; -.
DR ProteomicsDB; 277704; -.
DR Antibodypedia; 25218; 206 antibodies from 32 providers.
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 VEuPathDB; HostDB:ENSMUSG00000046179; -.
DR eggNOG; KOG2578; Eukaryota.
DR GeneTree; ENSGT00940000158651; -.
DR HOGENOM; CLU_014845_2_0_1; -.
DR InParanoid; Q58FA4; -.
DR OMA; NGHTEMC; -.
DR OrthoDB; 145070at2759; -.
DR PhylomeDB; Q58FA4; -.
DR TreeFam; TF105567; -.
DR Reactome; R-MMU-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
DR BioGRID-ORCS; 108961; 3 hits in 75 CRISPR screens.
DR ChiTaRS; E2f8; mouse.
DR PRO; PR:Q58FA4; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q58FA4; protein.
DR Bgee; ENSMUSG00000046179; Expressed in ileal epithelium and 173 other tissues.
DR Genevisible; Q58FA4; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IBA:GO_Central.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; IMP:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0033301; P:cell cycle comprising mitosis without cytokinesis; IMP:UniProtKB.
DR GO; GO:0060718; P:chorionic trophoblast cell differentiation; IMP:UniProtKB.
DR GO; GO:0048144; P:fibroblast proliferation; IDA:MGI.
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 by RNA polymerase II; 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 by RNA polymerase II; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0002040; P:sprouting angiogenesis; IMP:UniProtKB.
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; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR12081; PTHR12081; 1.
DR Pfam; PF02319; E2F_TDP; 2.
DR SMART; SM01372; E2F_TDP; 2.
DR SUPFAM; SSF46785; SSF46785; 2.
PE 1: Evidence at protein level;
KW Activator; Cell cycle; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..860
FT /note="Transcription factor E2F8"
FT /id="PRO_0000298910"
FT DNA_BIND 113..182
FT /evidence="ECO:0000255"
FT DNA_BIND 261..347
FT /evidence="ECO:0000255"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 38..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 407..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 532..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 745..803
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..433
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 579..600
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..803
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 102
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0AVK6"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0AVK6"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0AVK6"
FT MUTAGEN 118..119
FT /note="LG->EF: Loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:15722552"
FT MUTAGEN 266..267
FT /note="LR->EF: Loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:15722552"
FT CONFLICT 65
FT /note="M -> T (in Ref. 2; BAC33794)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="N -> Y (in Ref. 3; AAH86675)"
FT /evidence="ECO:0000305"
FT CONFLICT 155
FT /note="R -> Q (in Ref. 2; BAC39205)"
FT /evidence="ECO:0000305"
FT CONFLICT 209
FT /note="I -> T (in Ref. 2; BAC39205)"
FT /evidence="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
