E2F8_RAT
ID E2F8_RAT Reviewed; 860 AA.
AC F1LMN3; Q4FZV5;
DT 09-JAN-2013, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2013, sequence version 2.
DT 25-MAY-2022, entry version 64.
DE RecName: Full=Transcription factor E2F8;
DE Short=E2F-8;
GN Name=E2f8;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 271-860 (ISOFORM 2).
RC TISSUE=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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer and heterodimer: mainly forms homodimers and, to a
CC lesser extent, heterodimers with E2F8. Dimerization is important for
CC DNA-binding. Interacts with HIF1A (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=F1LMN3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=F1LMN3-2; Sequence=VSP_044620, VSP_044621;
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 -!- SIMILARITY: Belongs to the E2F/DP family. {ECO:0000305}.
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DR EMBL; BC099080; AAH99080.1; -; mRNA.
DR AlphaFoldDB; F1LMN3; -.
DR SMR; F1LMN3; -.
DR STRING; 10116.ENSRNOP00000036763; -.
DR iPTMnet; F1LMN3; -.
DR PhosphoSitePlus; F1LMN3; -.
DR PaxDb; F1LMN3; -.
DR UCSC; RGD:1308091; rat.
DR RGD; 1308091; E2f8.
DR eggNOG; KOG2578; Eukaryota.
DR InParanoid; F1LMN3; -.
DR TreeFam; TF105567; -.
DR Reactome; R-RNO-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
DR PRO; PR:F1LMN3; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
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:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0033301; P:cell cycle comprising mitosis without cytokinesis; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0060718; P:chorionic trophoblast cell differentiation; ISS:UniProtKB.
DR GO; GO:0070365; P:hepatocyte differentiation; ISS:UniProtKB.
DR GO; GO:0032466; P:negative regulation of cytokinesis; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0001890; P:placenta development; ISS:UniProtKB.
DR GO; GO:0032877; P:positive regulation of DNA endoreduplication; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; ISS: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; Alternative splicing; Cell cycle; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..860
FT /note="Transcription factor E2F8"
FT /id="PRO_0000420709"
FT DNA_BIND 112..181
FT /evidence="ECO:0000255"
FT DNA_BIND 261..347
FT /evidence="ECO:0000255"
FT REGION 1..114
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 533..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..20
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 74..114
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 533..571
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 582..600
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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 VAR_SEQ 570
FT /note="K -> KSSASCR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044620"
FT VAR_SEQ 765
FT /note="A -> AASVIP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044621"
SQ SEQUENCE 860 AA; 93023 MW; 91D4F75CE417F74C CRC64;
MENQKENLFS EPHKRGLVKS PLQESSKANV VLAEIQPDLG PLTTPTKPKE VSQGEPWTPT
ANLKMLISAV SPEIRSRDQK RGLSDNRSGL PEARDCLHEP QAKTNEKSQP SRKEKSLGLL
CHKFLARYPK YPNPAVNNDI CLDEVAEELD VERRRIYDIV NVLESLHMVS RLAKNRYTWH
GRHNLTKTLG TLKSVGEENK YAEQIMMIKR KEHEQEFDFI KSCGLEDHHV IKSTAGQNGH
SDMCFVELPG VEFRAASANS RKDKSLRVMS QKFVMLFLVS TPQIVSLEIA AKILIGEDHV
EDLDKSKFKT KIRRLYDIAN VLSSLDLIKK VHVTEERGRK PAFKWTGPEI SPNNSGSSPV
MPLTASLEAE QSAKENCAKN LFSTRGKPSF TRHPSLIKLV KSIENDRRKI SSAPSSPVKS
SKAESSQNSP PVPNKMAQLA AICKMQLEEQ SSEPRKRVKV NLTRSGHYKP LAPLDPAVNT
ELELLAPSLI QPLGMVPLIP SPLSSAVPVI LPQAPSGPSY AIYLQPAQAQ MLTPPHGLSP
TVCPTQSSNA TGSKDPTDAP TEKTATDATK PGSLQPAPER QGAKNRSKET TGDRGTKRTG
ALEDGGPGPI KKPKEDLKAL ENVPTPTTLF PSGYLIPLTQ CPSLGPDPML SNTENSGTLS
PNHRIYGSPI AGVIPVASSE LTAVNFPPFH VTPLKLMVSP TSMAAVPVGN SPALSSSHPA
PTQNPSSAIV NFTLQHLGLI SPGVQMSASP GPGAGTVPLS PRVEADNLSS RQGRATIHDS
PVLGQSQLNG QPVAGTGAQQ PVPVTPKGSQ LVAESFFRTP GGPTKPTSSS FMDFDGANKT
SFGTLFVPQR KLEVSTEDVH
