E2F1_HUMAN
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 03-AUG-2022, entry version 239.
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 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 [34]
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 [35]
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 [36]
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 [37]
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). {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:8336704,
CC 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; 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=25; 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=14; 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 -!- 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="http://atlasgeneticsoncology.org/Genes/E2F1ID40382ch20q11.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/e2f1/";
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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; 169.
DR ComplexPortal; CPX-155; RB1-E2F1-TFDP1 transcription repressor complex.
DR ComplexPortal; CPX-1971; E2F1-DP1 transcription factor complex.
DR CORUM; Q01094; -.
DR DIP; DIP-24227N; -.
DR ELM; Q01094; -.
DR IntAct; Q01094; 63.
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; Q01094; -.
DR PeptideAtlas; Q01094; -.
DR PRIDE; Q01094; -.
DR ProteomicsDB; 57915; -.
DR Antibodypedia; 3771; 1454 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 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; HVCTTQL; -.
DR OrthoDB; 1087250at2759; -.
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; 84 hits in 1109 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 150 other tissues.
DR Genevisible; Q01094; HS.
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:0000228; C:nuclear chromosome; 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:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
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:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; 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: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:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:ComplexPortal.
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:0071930; P:negative regulation of transcription involved in G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
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:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
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 GO; GO:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; IDA:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-templated; ISS:UniProtKB.
DR CDD; cd14660; E2F_DD; 1.
DR DisProt; DP01427; -.
DR Gene3D; 1.10.10.10; -; 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; PTHR12081; 1.
DR Pfam; PF16421; E2F_CC-MB; 1.
DR Pfam; PF02319; E2F_TDP; 1.
DR SMART; SM01372; E2F_TDP; 1.
DR SUPFAM; SSF144074; SSF144074; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Apoptosis; Cell cycle; DNA-binding;
KW Host-virus interaction; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; 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 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 R-
FT 120 and R-125."
FT /evidence="ECO:0000269|PubMed:10675335"
FT MUTAGEN 120
FT /note="K->R: Abolishes acetylation; when associated with R-
FT 117 and R-125."
FT /evidence="ECO:0000269|PubMed:10675335"
FT MUTAGEN 125
FT /note="K->R: Abolishes acetylation; when associated with R-
FT 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 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
