ID E2F1_HUMAN Reviewed; 437 AA. AC Q01094; Q13143; Q92768; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 1. DT 27-MAR-2024, entry version 248. DE RecName: Full=Transcription factor E2F1 {ECO:0000303|PubMed:8964493}; DE Short=E2F-1 {ECO:0000303|PubMed:8964493}; DE AltName: Full=PBR3; DE AltName: Full=Retinoblastoma-associated protein 1 {ECO:0000303|PubMed:1638635}; DE Short=RBAP-1 {ECO:0000303|PubMed:1638635}; DE AltName: Full=Retinoblastoma-binding protein 3 {ECO:0000303|PubMed:1638634}; DE Short=RBBP-3 {ECO:0000303|PubMed:1638634}; DE AltName: Full=pRB-binding protein E2F-1; GN Name=E2F1 {ECO:0000303|PubMed:8964493, ECO:0000312|HGNC:HGNC:3113}; GN Synonyms=RBBP3 {ECO:0000303|PubMed:1638634}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1638634; DOI=10.1016/0092-8674(92)90107-n; RA Helin K., Lees J.A., Vidal M., Dyson N.J., Harlow E., Fattaey A.; RT "A cDNA encoding a pRB-binding protein with properties of the transcription RT factor E2F."; RL Cell 70:337-350(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1638635; DOI=10.1016/0092-8674(92)90108-o; RA Kaelin W.G. Jr., Krek W., Sellers W.R., Decaprio J.A., Ajchenbaum F., RA Fuchs C.S., Chittenden T., Li Y., Farnham P.J., Blanar M.A., RA Livingston D.M., Flemington E.K.; RT "Expression cloning of a cDNA encoding a retinoblastoma-binding protein RT with E2F-like properties."; RL Cell 70:351-364(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1448092; DOI=10.1128/mcb.12.12.5620-5631.1992; RA Shan B., Zhu X., Chen P.L., Durfee T., Yang Y., Sharp D., Lee W.H.; RT "Molecular cloning of cellular genes encoding retinoblastoma-associated RT proteins: identification of a gene with properties of the transcription RT factor E2F."; RL Mol. Cell. Biol. 12:5620-5631(1992). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8964493; DOI=10.1016/0378-1119(96)00184-9; RA Neuman E., Sellers W.R.S., McNeil J.A., Lawrence J.B., Kaelin W.G. Jr.; RT "Structure and partial genomic sequence of the human E2F1 gene."; RL Gene 173:163-169(1996). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-252; MET-276; ASN-311 RP AND SER-393. RG NIEHS SNPs program; RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas, and Skin; 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 [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-111. RX PubMed=7958836; DOI=10.1101/gad.8.13.1514; RA Johnson D.G., Ohtani K., Nevins J.R.; RT "Autoregulatory control of E2F1 expression in response to positive and RT negative regulators of cell cycle progression."; RL Genes Dev. 8:1514-1525(1994). RN [9] RP INTERACTION WITH RB1. RX PubMed=8336704; DOI=10.1128/mcb.13.8.4588-4599.1993; RA Zacksenhaus E., Bremner R., Phillips R.A., Gallie B.L.; RT "A bipartite nuclear localization signal in the retinoblastoma gene product RT and its importance for biological activity."; RL Mol. Cell. Biol. 13:4588-4599(1993). RN [10] RP TRANSACTIVATION INHIBITION, AND MUTAGENESIS OF TYR-411. RX PubMed=8413249; DOI=10.1128/mcb.13.10.6501-6508.1993; RA Helin K., Harlow E., Fattaey A.; RT "Inhibition of E2F-1 transactivation by direct binding of the RT retinoblastoma protein."; RL Mol. Cell. Biol. 13:6501-6508(1993). RN [11] RP DOMAIN CYCLIN A:CDK2 BINDING. RX PubMed=8033208; DOI=10.1016/0092-8674(94)90582-7; RA Krek W., Ewen M.E., Shirodkar S., Arany Z., Kaelin W.G. Jr., RA Livingston D.M.; RT "Negative regulation of the growth-promoting transcription factor E2F-1 by RT a stably bound cyclin A-dependent protein kinase."; RL Cell 78:161-172(1994). RN [12] RP DIFFERENTIAL REGULATION BY CYCLIN/CDK2 KINASES. RX PubMed=7958856; DOI=10.1101/gad.8.15.1772; RA Dynlacht B.D., Flores O., Lees J.A., Harlow E.; RT "Differential regulation of E2F transactivation by cyclin/cdk2 complexes."; RL Genes Dev. 8:1772-1786(1994). RN [13] RP INHIBITION OF DNA-BINDING. RX PubMed=7969176; DOI=10.1128/mcb.14.12.8420-8431.1994; RA Xu M., Sheppard K.-A., Peng C.-Y., Yee A.S., Piwnica-Worms H.; RT "Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding RT activity of E2F-1/DP-1 by phosphorylation."; RL Mol. Cell. Biol. 14:8420-8431(1994). RN [14] RP FUNCTION IN APOPTOSIS. RX PubMed=8170954; DOI=10.1073/pnas.91.9.3602; RA Wu X., Levine A.J.; RT "P53 and E2F-1 cooperate to mediate apoptosis."; RL Proc. Natl. Acad. Sci. U.S.A. 91:3602-3606(1994). RN [15] RP INTERACTION WITH HHV-5 PROTEIN UL123. RX PubMed=7494286; DOI=10.1128/jvi.69.12.7759-7767.1995; RA Margolis M.J., Pajovic S., Wong E.L., Wade M., Jupp R., Nelson J.A., RA Azizkhan J.C.; RT "Interaction of the 72-kilodalton human cytomegalovirus IE1 gene product RT with E2F1 coincides with E2F-dependent activation of dihydrofolate RT reductase transcription."; RL J. Virol. 69:7759-7767(1995). RN [16] RP PHOSPHORYLATION. RX PubMed=7838523; RA Kitagawa M., Higashi H., Suzuki-Takahashi I., Segawa K., Hanks S.K., RA Taya Y., Nishimura S., Okuyama A.; RT "Phosphorylation of E2F-1 by cyclin A-cdk2."; RL Oncogene 10:229-236(1995). RN [17] RP REGULATION BY CYCLIN-DEPENDENT KINASES. RX PubMed=9199321; DOI=10.1128/mcb.17.7.3867; RA Dynlacht B.D., Moberg K., Lees J.A., Harlow E., Zhu L.; RT "Specific regulation of E2F family members by cyclin-dependent kinases."; RL Mol. Cell. Biol. 17:3867-3875(1997). RN [18] RP INTERACTION WITH ARID3A. RX PubMed=9780002; DOI=10.1038/sj.onc.1202163; RA Suzuki M., Okuyama S., Okamoto S., Shirasuna K., Nakajima T., Hachiya T., RA Nojima H., Sekiya S., Oda K.; RT "A novel E2F binding protein with Myc-type HLH motif stimulates E2F- RT dependent transcription by forming a heterodimer."; RL Oncogene 17:853-865(1998). RN [19] RP ACETYLATION AT LYS-117; LYS-120 AND LYS-125, DNA-BINDING, INTERACTION WITH RP KAT2B, FUNCTION, AND MUTAGENESIS OF LYS-117; LYS-120 AND LYS-125. RX PubMed=10675335; DOI=10.1093/emboj/19.4.662; RA Martinez-Balbas M.A., Bauer U.M., Nielsen S.J., Brehm A., Kouzarides T.; RT "Regulation of E2F1 activity by acetylation."; RL EMBO J. 19:662-671(2000). RN [20] RP INTERACTION WITH TRRAP. RX PubMed=11418595; DOI=10.1074/jbc.m102067200; RA Lang S.E., McMahon S.B., Cole M.D., Hearing P.; RT "E2F transcriptional activation requires TRRAP and GCN5 cofactors."; RL J. Biol. Chem. 276:32627-32634(2001). RN [21] RP INTERACTION WITH TOPBP1. RX PubMed=12697828; DOI=10.1128/mcb.23.9.3287-3304.2003; RA Liu K., Lin F.-T., Ruppert J.M., Lin W.-C.; RT "Regulation of E2F1 by BRCT domain-containing protein TopBP1."; RL Mol. Cell. Biol. 23:3287-3304(2003). RN [22] RP FUNCTION IN TRANSCRIPTION REGULATION, FUNCTION IN APOPTOSIS, RP PHOSPHORYLATION AT SER-364 BY CHEK2, AND MUTAGENESIS OF SER-364. RX PubMed=12717439; DOI=10.1038/ncb974; RA Stevens C., Smith L., La Thangue N.B.; RT "Chk2 activates E2F-1 in response to DNA damage."; RL Nat. Cell Biol. 5:401-409(2003). RN [23] RP INTERACTION WITH RB1 AND TFDP1. RX PubMed=16360038; DOI=10.1016/j.cell.2005.09.044; RA Rubin S.M., Gall A.-L., Zheng N., Pavletich N.P.; RT "Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for RT phosphorylation-induced E2F release."; RL Cell 123:1093-1106(2005). RN [24] RP INTERACTION WITH EAPP. RX PubMed=15716352; DOI=10.1091/mbc.e04-11-0975; RA Novy M., Pohn R., Andorfer P., Novy-Weiland T., Galos B., Schwarzmayr L., RA Rotheneder H.; RT "EAPP, a novel E2F binding protein that modulates E2F-dependent RT transcription."; RL Mol. Biol. Cell 16:2181-2190(2005). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [26] RP FUNCTION, PHOSPHORYLATION AT SER-403 AND THR-433, AND MUTAGENESIS OF RP SER-403 AND THR-433. RX PubMed=17050006; DOI=10.1016/j.bbamcr.2006.09.015; RA Garcia-Alvarez G., Ventura V., Ros O., Aligue R., Gil J., Tauler A.; RT "Glycogen synthase kinase-3beta binds to E2F1 and regulates its RT transcriptional activity."; RL Biochim. Biophys. Acta 1773:375-382(2007). RN [27] RP INTERACTION WITH HDAC1 AND TRIM28, FUNCTION, ACETYLATION, AND RP DEACETYLATION. RX PubMed=17704056; DOI=10.1074/jbc.m704757200; RA Wang C., Rauscher F.J. III, Cress W.D., Chen J.; RT "Regulation of E2F1 function by the nuclear corepressor KAP1."; RL J. Biol. Chem. 282:29902-29909(2007). RN [28] RP FUNCTION. RX PubMed=18625225; DOI=10.1016/j.febslet.2008.07.009; RA Wang C., Xiao Y., Hu Z., Chen Y., Liu N., Hu G.; RT "PEG10 directly regulated by E2Fs might have a role in the development of RT hepatocellular carcinoma."; RL FEBS Lett. 582:2793-2798(2008). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [31] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RRP1B. RX PubMed=20040599; DOI=10.1074/jbc.m109.072074; RA Paik J.C., Wang B., Liu K., Lue J.K., Lin W.C.; RT "Regulation of E2F1-induced apoptosis by the nucleolar protein RRP1B."; RL J. Biol. Chem. 285:6348-6363(2010). RN [32] RP FUNCTION, INTERACTION WITH CEBPA, AND MUTAGENESIS OF LEU-132 AND TYR-411. RX PubMed=20176812; DOI=10.1128/mcb.01619-09; RA Zaragoza K., Begay V., Schuetz A., Heinemann U., Leutz A.; RT "Repression of transcriptional activity of C/EBPalpha by E2F-dimerization RT partner complexes."; RL Mol. Cell. Biol. 30:2293-2304(2010). RN [33] RP METHYLATION AT LYS-185, AND MUTAGENESIS OF LYS-185. RX PubMed=20603083; DOI=10.1016/j.molcel.2010.06.006; RA Kontaki H., Talianidis I.; RT "Lysine methylation regulates E2F1-induced cell death."; RL Mol. Cell 39:152-160(2010). RN [34] RP INTERACTION WITH BIRC2, AND ACTIVITY REGULATION. RX PubMed=21653699; DOI=10.1074/jbc.m110.191239; RA Cartier J., Berthelet J., Marivin A., Gemble S., Edmond V., Plenchette S., RA Lagrange B., Hammann A., Dupoux A., Delva L., Eymin B., Solary E., RA Dubrez L.; RT "Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 RT transcription factor-mediated control of cyclin transcription."; RL J. Biol. Chem. 286:26406-26417(2011). RN [35] RP INTERACTION WITH KMT2E AND HCFC1. RX PubMed=23629655; DOI=10.1074/jbc.m112.439729; RA Zhou P., Wang Z., Yuan X., Zhou C., Liu L., Wan X., Zhang F., Ding X., RA Wang C., Xiong S., Wang Z., Yuan J., Li Q., Zhang Y.; RT "Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle progression RT and E2F1-responsive gene expression via association with host cell factor-1 RT (HCF-1)."; RL J. Biol. Chem. 288:17532-17543(2013). RN [36] RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, DEUBIQUITINATION, RP PHOSPHORYLATION AT SER-403, AND MUTAGENESIS OF SER-403. RX PubMed=28992046; DOI=10.1093/jmcb/mjx034; RA Wang D., Zhao J., Li S., Wei J., Nan L., Mallampalli R.K., RA Weathington N.M., Ma H., Zhao Y.; RT "Phosphorylated E2F1 is stabilized by nuclear USP11 to drive Peg10 gene RT expression and activate lung epithelial cells."; RL J. Mol. Cell Biol. 10:60-73(2018). RN [37] RP INTERACTION WITH DCAF5 AND L3MBTL3, AND MUTAGENESIS OF LYS-185. RX PubMed=29691401; DOI=10.1038/s41467-018-04019-9; RA Leng F., Yu J., Zhang C., Alejo S., Hoang N., Sun H., Lu F., Zhang H.; RT "Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and RT CRL4-DCAF5 ubiquitin ligase."; RL Nat. Commun. 9:1641-1641(2018). RN [38] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 87-95. RX PubMed=12501191; DOI=10.1021/bi0268910; RA Lowe E.D., Tews I., Cheng K.Y., Brown N.R., Gul S., Noble M.E.M., RA Gamblin S.J., Johnson L.N.; RT "Specificity determinants of recruitment peptides bound to phospho- RT CDK2/cyclin A."; RL Biochemistry 41:15625-15634(2002). RN [39] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 409-426 IN COMPLEX WITH RB1. RX PubMed=12598654; DOI=10.1073/pnas.0436813100; RA Xiao B., Spencer J., Clements A., Ali-Khan N., Mittnacht S., Broceno C., RA Burghammer M., Perrakis A., Marmorstein R., Gamblin S.J.; RT "Crystal structure of the retinoblastoma tumor suppressor protein bound to RT E2F and the molecular basis of its regulation."; RL Proc. Natl. Acad. Sci. U.S.A. 100:2363-2368(2003). CC -!- FUNCTION: Transcription activator that binds DNA cooperatively with DP CC proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in CC the promoter region of a number of genes whose products are involved in CC cell cycle regulation or in DNA replication (PubMed:10675335, CC PubMed:12717439, PubMed:17704056, PubMed:17050006, PubMed:18625225, CC PubMed:28992046). The DRTF1/E2F complex functions in the control of CC cell-cycle progression from G1 to S phase (PubMed:10675335, CC PubMed:12717439, PubMed:17704056). E2F1 binds preferentially RB1 in a CC cell-cycle dependent manner (PubMed:10675335, PubMed:12717439, CC PubMed:17704056). It can mediate both cell proliferation and TP53/p53- CC dependent apoptosis (PubMed:8170954). Blocks adipocyte differentiation CC by binding to specific promoters repressing CEBPA binding to its target CC gene promoters (PubMed:20176812). Directly activates transcription of CC PEG10 (PubMed:17050006, PubMed:18625225, PubMed:28992046). Positively CC regulates transcription of RRP1B (PubMed:20040599). CC {ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:12717439, CC ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:17704056, CC ECO:0000269|PubMed:18625225, ECO:0000269|PubMed:20040599, CC ECO:0000269|PubMed:20176812, ECO:0000269|PubMed:28992046, CC ECO:0000269|PubMed:8170954}. CC -!- ACTIVITY REGULATION: BIRC2/c-IAP1 stimulates its transcriptional CC activity. {ECO:0000269|PubMed:21653699}. CC -!- SUBUNIT: Component of the DRTF1/E2F transcription factor complex. Forms CC heterodimers with DP family members. The E2F1 complex binds CC specifically hypophosphorylated retinoblastoma protein RB1 CC (PubMed:8336704). During the cell cycle, RB1 becomes phosphorylated in CC mid-to-late G1 phase, detaches from the DRTF1/E2F complex, rendering CC E2F transcriptionally active. Viral oncoproteins, notably E1A, T- CC antigen and HPV E7, are capable of sequestering RB1, thus releasing the CC active complex. Interacts with TRRAP, which probably mediates its CC interaction with histone acetyltransferase complexes, leading to CC transcription activation. Binds TOPBP1 and EAPP. Interacts with ARID3A. CC Interacts with TRIM28; the interaction inhibits E2F1 acetylation CC through recruiting HDAC1 and represses its transcriptional activity. CC Interaction with KAT2B; the interaction acetylates E2F1 enhancing its CC DNA-binding and transcriptional activity. Interacts with BIRC2/c-IAP1 CC (via BIR domains). The complex TFDP1:E2F1 interacts with CEBPA; the CC interaction prevents CEBPA binding to target genes promoters and CC represses its transcriptional activity (PubMed:20176812). Interacts CC with RRP1B (PubMed:20040599). Interacts with HCFC1 (PubMed:23629655). CC Interacts with KMT2E; the interaction is probably indirect and is CC mediated via HCFC1 (PubMed:23629655). Interacts with DCAF5 and L3MBTL3; CC the interaction requires methylation at Lys-185 and is necessary to CC target E2F1 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase CC complex (PubMed:29691401). {ECO:0000250|UniProtKB:Q61501, CC ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:11418595, CC ECO:0000269|PubMed:12598654, ECO:0000269|PubMed:12697828, CC ECO:0000269|PubMed:15716352, ECO:0000269|PubMed:16360038, CC ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:20040599, CC ECO:0000269|PubMed:20176812, ECO:0000269|PubMed:21653699, CC ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:29691401, CC ECO:0000269|PubMed:8336704, ECO:0000269|PubMed:9780002}. CC -!- SUBUNIT: (Microbial infection) Interacts with human CC cytomegalovirus/HHV-5 protein UL123. {ECO:0000269|PubMed:7494286}. CC -!- INTERACTION: CC Q01094; P05067: APP; NbExp=3; IntAct=EBI-448924, EBI-77613; CC Q01094; Q14201: BTG3; NbExp=3; IntAct=EBI-448924, EBI-948192; CC Q01094; P49336: CDK8; NbExp=3; IntAct=EBI-448924, EBI-394377; CC Q01094; Q92466: DDB2; NbExp=2; IntAct=EBI-448924, EBI-1176171; CC Q01094; Q13547: HDAC1; NbExp=2; IntAct=EBI-448924, EBI-301834; CC Q01094; Q92830: KAT2A; NbExp=3; IntAct=EBI-448924, EBI-477622; CC Q01094; Q96JM7: L3MBTL3; NbExp=2; IntAct=EBI-448924, EBI-2686809; CC Q01094; Q8NEM0: MCPH1; NbExp=6; IntAct=EBI-448924, EBI-1565483; CC Q01094; Q9Y618: NCOR2; NbExp=2; IntAct=EBI-448924, EBI-80830; CC Q01094; P09874: PARP1; NbExp=3; IntAct=EBI-448924, EBI-355676; CC Q01094; Q96IZ0: PAWR; NbExp=2; IntAct=EBI-448924, EBI-595869; CC Q01094; O14744: PRMT5; NbExp=8; IntAct=EBI-448924, EBI-351098; CC Q01094; P06400: RB1; NbExp=29; IntAct=EBI-448924, EBI-491274; CC Q01094; Q14684: RRP1B; NbExp=10; IntAct=EBI-448924, EBI-372051; CC Q01094; Q96EB6: SIRT1; NbExp=3; IntAct=EBI-448924, EBI-1802965; CC Q01094; P08047: SP1; NbExp=2; IntAct=EBI-448924, EBI-298336; CC Q01094; P42224: STAT1; NbExp=2; IntAct=EBI-448924, EBI-1057697; CC Q01094; Q14186: TFDP1; NbExp=17; IntAct=EBI-448924, EBI-749713; CC Q01094; Q92547: TOPBP1; NbExp=3; IntAct=EBI-448924, EBI-308302; CC Q01094; O95361: TRIM16; NbExp=2; IntAct=EBI-448924, EBI-727384; CC Q01094; P03129: E7; Xeno; NbExp=2; IntAct=EBI-448924, EBI-866453; CC Q01094; Q923E4: Sirt1; Xeno; NbExp=3; IntAct=EBI-448924, EBI-1802585; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20040599, CC ECO:0000269|PubMed:28992046}. CC -!- PTM: Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase CC (PubMed:12717439, PubMed:7838523). Phosphorylation at Ser-364 by CHEK2 CC stabilizes E2F1 upon DNA damage and regulates its effect on CC transcription and apoptosis (PubMed:12717439). Phosphorylation at Ser- CC 403 by GSK3B promotes interaction with USP11, leading to its CC deubiquitination and stabilization (PubMed:28992046). CC {ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:28992046, CC ECO:0000269|PubMed:7838523}. CC -!- PTM: Ubiquitinated via 'Lys-63'-linked ubiquitin, leading to its CC degradation (PubMed:28992046). Deubiquitinated by USP11 follwong CC phosphorylation by GSK3B, promoting its stability (PubMed:28992046). CC {ECO:0000269|PubMed:28992046}. CC -!- PTM: Acetylation stimulates DNA-binding. Enhanced under stress CC conditions such as DNA damage and inhibited by retinoblastoma protein CC RB1. Regulated by KAP1/TRIM28 which recruits HDAC1 to E2F1 resulting in CC deacetylation. Acetylated by P/CAF/KAT2B. {ECO:0000269|PubMed:10675335, CC ECO:0000269|PubMed:17704056}. CC -!- PTM: Methylation at Lys-185 by SETD7 promotes E2F1 ubiquitin-dependent CC proteasomal degradation. {ECO:0000269|PubMed:20603083, CC ECO:0000269|PubMed:29691401}. CC -!- SIMILARITY: Belongs to the E2F/DP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB24289.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40382/E2F1"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/e2f1/"; 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; M96577; AAA35782.1; -; mRNA. DR EMBL; U47677; AAC50719.1; -; Genomic_DNA. DR EMBL; U47675; AAC50719.1; JOINED; Genomic_DNA. DR EMBL; U47676; AAC50719.1; JOINED; Genomic_DNA. DR EMBL; S49592; AAB24289.1; ALT_INIT; mRNA. DR EMBL; AF516106; AAM47604.1; -; Genomic_DNA. DR EMBL; AL121906; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC050369; AAH50369.1; -; mRNA. DR EMBL; BC058902; AAH58902.1; -; mRNA. DR EMBL; S74230; AAD14150.1; -; Genomic_DNA. DR CCDS; CCDS13224.1; -. DR PIR; JC4929; JC4929. DR RefSeq; NP_005216.1; NM_005225.2. DR PDB; 1H24; X-ray; 2.50 A; E=87-95. DR PDB; 1O9K; X-ray; 2.60 A; P/Q/R/S=409-426. DR PDB; 2AZE; X-ray; 2.55 A; B=200-301. DR PDB; 5M9N; X-ray; 1.95 A; C=104-120. DR PDB; 5M9O; X-ray; 1.45 A; B=108-116. DR PDB; 6G0P; X-ray; 1.30 A; B=114-129. DR PDB; 6ULS; X-ray; 1.50 A; B=114-123. DR PDBsum; 1H24; -. DR PDBsum; 1O9K; -. DR PDBsum; 2AZE; -. DR PDBsum; 5M9N; -. DR PDBsum; 5M9O; -. DR PDBsum; 6G0P; -. DR PDBsum; 6ULS; -. DR AlphaFoldDB; Q01094; -. DR SASBDB; Q01094; -. DR SMR; Q01094; -. DR BioGRID; 108201; 170. DR ComplexPortal; CPX-155; RB1-E2F1-DP1 transcriptional repressor complex. DR ComplexPortal; CPX-1971; E2F1-DP1 transcription factor complex. DR CORUM; Q01094; -. DR DIP; DIP-24227N; -. DR ELM; Q01094; -. DR IntAct; Q01094; 113. DR MINT; Q01094; -. DR STRING; 9606.ENSP00000345571; -. DR ChEMBL; CHEMBL4382; -. DR iPTMnet; Q01094; -. DR PhosphoSitePlus; Q01094; -. DR BioMuta; E2F1; -. DR DMDM; 400928; -. DR MassIVE; Q01094; -. DR MaxQB; Q01094; -. DR PaxDb; 9606-ENSP00000345571; -. DR PeptideAtlas; Q01094; -. DR ProteomicsDB; 57915; -. DR Antibodypedia; 3771; 1695 antibodies from 48 providers. DR DNASU; 1869; -. DR Ensembl; ENST00000343380.6; ENSP00000345571.5; ENSG00000101412.13. DR GeneID; 1869; -. DR KEGG; hsa:1869; -. DR MANE-Select; ENST00000343380.6; ENSP00000345571.5; NM_005225.3; NP_005216.1. DR UCSC; uc002wzu.5; human. DR AGR; HGNC:3113; -. DR CTD; 1869; -. DR DisGeNET; 1869; -. DR GeneCards; E2F1; -. DR HGNC; HGNC:3113; E2F1. DR HPA; ENSG00000101412; Tissue enhanced (bone). DR MIM; 189971; gene. DR neXtProt; NX_Q01094; -. DR OpenTargets; ENSG00000101412; -. DR PharmGKB; PA152; -. DR VEuPathDB; HostDB:ENSG00000101412; -. DR eggNOG; KOG2577; Eukaryota. DR GeneTree; ENSGT00940000159472; -. DR HOGENOM; CLU_032091_0_1_1; -. DR InParanoid; Q01094; -. DR OMA; HVMEQQI; -. DR OrthoDB; 1761at2759; -. DR PhylomeDB; Q01094; -. DR TreeFam; TF105566; -. DR PathwayCommons; Q01094; -. DR Reactome; R-HSA-111448; Activation of NOXA and translocation to mitochondria. DR Reactome; R-HSA-113501; Inhibition of replication initiation of damaged DNA by RB1/E2F1. DR Reactome; R-HSA-1362277; Transcription of E2F targets under negative control by DREAM complex. DR Reactome; R-HSA-1362300; Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1. DR Reactome; R-HSA-139915; Activation of PUMA and translocation to mitochondria. DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-HSA-2559585; Oncogene Induced Senescence. DR Reactome; R-HSA-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest. DR Reactome; R-HSA-68911; G2 Phase. DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition. DR Reactome; R-HSA-69205; G1/S-Specific Transcription. DR Reactome; R-HSA-69231; Cyclin D associated events in G1. DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry. DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. DR Reactome; R-HSA-9661069; Defective binding of RB1 mutants to E2F1,(E2F2, E2F3). DR SignaLink; Q01094; -. DR SIGNOR; Q01094; -. DR BioGRID-ORCS; 1869; 91 hits in 1191 CRISPR screens. DR ChiTaRS; E2F1; human. DR EvolutionaryTrace; Q01094; -. DR GeneWiki; E2F1; -. DR GenomeRNAi; 1869; -. DR Pharos; Q01094; Tbio. DR PRO; PR:Q01094; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q01094; Protein. DR Bgee; ENSG00000101412; Expressed in ganglionic eminence and 152 other cell types or tissues. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0035189; C:Rb-E2F complex; IDA:BHF-UCL. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal. DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0001216; F:DNA-binding transcription activator activity; IDA:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:UniProtKB. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:0060090; F:molecular adaptor activity; EXP:DisProt. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0043276; P:anoikis; IEA:Ensembl. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:UniProtKB. DR GO; GO:0006351; P:DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0030900; P:forebrain development; IEA:Ensembl. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central. DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IEA:Ensembl. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:UniProtKB. DR GO; GO:1990086; P:lens fiber cell apoptotic process; IEA:Ensembl. DR GO; GO:0048255; P:mRNA stabilization; IDA:BHF-UCL. DR GO; GO:0043392; P:negative regulation of DNA binding; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB. DR GO; GO:0070345; P:negative regulation of fat cell proliferation; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR CDD; cd14660; E2F_DD; 1. DR DisProt; DP01427; -. DR Gene3D; 6.10.250.540; -; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR IDEAL; IID00064; -. DR InterPro; IPR015633; E2F. DR InterPro; IPR037241; E2F-DP_heterodim. DR InterPro; IPR032198; E2F_CC-MB. 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; TRANSCRIPTION FACTOR E2F; 1. DR PANTHER; PTHR12081:SF43; TRANSCRIPTION FACTOR E2F1; 1. DR Pfam; PF16421; E2F_CC-MB; 1. DR Pfam; PF02319; E2F_TDP; 1. DR SMART; SM01372; E2F_TDP; 1. DR SUPFAM; SSF144074; E2F-DP heterodimerization region; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR Genevisible; Q01094; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Apoptosis; Cell cycle; DNA-binding; KW Host-virus interaction; Methylation; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..437 FT /note="Transcription factor E2F1" FT /id="PRO_0000219461" FT DNA_BIND 110..194 FT /evidence="ECO:0000255" FT REGION 42..87 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 67..108 FT /note="Cyclin A:CDK2 binding" FT /evidence="ECO:0000269|PubMed:8033208" FT REGION 89..191 FT /note="Interaction with BIRC2/c-IAP1" FT /evidence="ECO:0000269|PubMed:21653699" FT REGION 101..128 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 153..174 FT /note="Leucine-zipper" FT REGION 192..382 FT /note="Required for interaction with TRIM28" FT /evidence="ECO:0000269|PubMed:17704056" FT REGION 195..284 FT /note="Dimerization" FT /evidence="ECO:0000255" FT REGION 300..349 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 368..437 FT /note="Transactivation" FT REGION 409..426 FT /note="RB1 binding" FT /evidence="ECO:0000269|PubMed:12598654" FT MOTIF 158..194 FT /note="DEF box" FT MOD_RES 117 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:10675335" FT MOD_RES 120 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:10675335" FT MOD_RES 125 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:10675335" FT MOD_RES 185 FT /note="N6-methyllysine; by SETD7" FT /evidence="ECO:0000269|PubMed:20603083" FT MOD_RES 364 FT /note="Phosphoserine; by CHEK2" FT /evidence="ECO:0000305|PubMed:12717439" FT MOD_RES 375 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332" FT MOD_RES 403 FT /note="Phosphoserine; by GSK3-beta" FT /evidence="ECO:0000269|PubMed:17050006, FT ECO:0000269|PubMed:28992046" FT MOD_RES 433 FT /note="Phosphothreonine; by GSK3-beta" FT /evidence="ECO:0000269|PubMed:17050006" FT VARIANT 200 FT /note="G -> S (in dbSNP:rs35385772)" FT /id="VAR_048907" FT VARIANT 252 FT /note="R -> H (in dbSNP:rs3213172)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_013607" FT VARIANT 276 FT /note="V -> M (in dbSNP:rs3213173)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_013608" FT VARIANT 311 FT /note="T -> N (in dbSNP:rs3213174)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_013609" FT VARIANT 393 FT /note="G -> S (in dbSNP:rs3213176)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_013610" FT MUTAGEN 117 FT /note="K->R: Abolishes acetylation; when associated with FT R-120 and R-125." FT /evidence="ECO:0000269|PubMed:10675335" FT MUTAGEN 120 FT /note="K->R: Abolishes acetylation; when associated with FT R-117 and R-125." FT /evidence="ECO:0000269|PubMed:10675335" FT MUTAGEN 125 FT /note="K->R: Abolishes acetylation; when associated with FT R-117 and R-120." FT /evidence="ECO:0000269|PubMed:10675335" FT MUTAGEN 132 FT /note="L->E: Abolishes interaction with and repression of FT CEBPA and inhibition of adipogenesis." FT /evidence="ECO:0000269|PubMed:20176812" FT MUTAGEN 185 FT /note="K->R: Abrogates methylation by SETD7. Loss of FT interaction with L3MBTL3. Loss of ubiquitination by the FT CRL4-DCAF5 E3 ubiquitin ligase complex." FT /evidence="ECO:0000269|PubMed:20603083, FT ECO:0000269|PubMed:29691401" FT MUTAGEN 364 FT /note="S->A: Abrogates in vitro phosphorylation by CHEK2 FT and CHEK2-dependent stabilization of E2F1 upon DNA damage." FT /evidence="ECO:0000269|PubMed:12717439" FT MUTAGEN 403 FT /note="S->A: Decreased phosphorylation by GSK3B, leading to FT abolished interaction with USP11 and subsequent FT deubiquitination." FT /evidence="ECO:0000269|PubMed:17050006, FT ECO:0000269|PubMed:28992046" FT MUTAGEN 411 FT /note="Y->C: No retinoblastoma protein binding. No effect FT on interaction with and repression of CEBPA." FT /evidence="ECO:0000269|PubMed:20176812, FT ECO:0000269|PubMed:8413249" FT MUTAGEN 433 FT /note="T->A: Decreased phosphorylation by GSK3B." FT /evidence="ECO:0000269|PubMed:17050006" FT CONFLICT 89..111 FT /note="KRRLDLETDHQYLAESSGPARGR -> RTPGTPRRQRRLCPPRRPGRAPC FT (in Ref. 8; AAD14150)" FT /evidence="ECO:0000305" FT CONFLICT 313 FT /note="S -> Y (in Ref. 4; AAC50719)" FT /evidence="ECO:0000305" FT CONFLICT 322 FT /note="N -> T (in Ref. 4; AAC50719)" FT /evidence="ECO:0000305" FT CONFLICT 329 FT /note="T -> N (in Ref. 4; AAC50719)" FT /evidence="ECO:0000305" FT HELIX 202..236 FT /evidence="ECO:0007829|PDB:2AZE" FT HELIX 238..243 FT /evidence="ECO:0007829|PDB:2AZE" FT STRAND 245..247 FT /evidence="ECO:0007829|PDB:2AZE" FT HELIX 248..252 FT /evidence="ECO:0007829|PDB:2AZE" FT TURN 257..259 FT /evidence="ECO:0007829|PDB:2AZE" FT STRAND 260..266 FT /evidence="ECO:0007829|PDB:2AZE" FT STRAND 272..277 FT /evidence="ECO:0007829|PDB:2AZE" FT STRAND 282..287 FT /evidence="ECO:0007829|PDB:2AZE" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:2AZE" FT STRAND 294..296 FT /evidence="ECO:0007829|PDB:2AZE" FT HELIX 421..424 FT /evidence="ECO:0007829|PDB:1O9K" SQ SEQUENCE 437 AA; 46920 MW; 003B3F654F0C60DF CRC64; MALAGAPAGG PCAPALEALL GAGALRLLDS SQIVIISAAQ DASAPPAPTG PAAPAAGPCD PDLLLFATPQ APRPTPSAPR PALGRPPVKR RLDLETDHQY LAESSGPARG RGRHPGKGVK SPGEKSRYET SLNLTTKRFL ELLSHSADGV VDLNWAAEVL KVQKRRIYDI TNVLEGIQLI AKKSKNHIQW LGSHTTVGVG GRLEGLTQDL RQLQESEQQL DHLMNICTTQ LRLLSEDTDS QRLAYVTCQD LRSIADPAEQ MVMVIKAPPE TQLQAVDSSE NFQISLKSKQ GPIDVFLCPE ETVGGISPGK TPSQEVTSEE ENRATDSATI VSPPPSSPPS SLTTDPSQSL LSLEQEPLLS RMGSLRAPVD EDRLSPLVAA DSLLEHVRED FSGLLPEEFI SLSPPHEALD YHFGLEEGEG IRDLFDCDFG DLTPLDF //