E4F1_HUMAN
ID E4F1_HUMAN Reviewed; 784 AA.
AC Q66K89; A8K2R4; O00146;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Transcription factor E4F1;
DE EC=2.3.2.27 {ECO:0000269|PubMed:17110336};
DE AltName: Full=E4F transcription factor 1;
DE AltName: Full=Putative E3 ubiquitin-protein ligase E4F1;
DE AltName: Full=RING-type E3 ubiquitin transferase E4F1 {ECO:0000305};
DE AltName: Full=Transcription factor E4F;
DE AltName: Full=p120E4F;
DE AltName: Full=p50E4F;
GN Name=E4F1; Synonyms=E4F;
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], FUNCTION, PROTEOLYTIC PROCESSING,
RP PHOSPHORYLATION, DNA-BINDING, AND VARIANT HIS-167.
RC TISSUE=Cervix carcinoma;
RX PubMed=9121437; DOI=10.1128/mcb.17.4.1890;
RA Fernandes E.R., Rooney R.J.;
RT "The adenovirus E1A-regulated transcription factor E4F is generated from
RT the human homolog of nuclear factor phiAP3.";
RL Mol. Cell. Biol. 17:1890-1903(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-167.
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT HIS-167.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-167.
RC TISSUE=Uterus;
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 [6]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9530632; DOI=10.1007/s003359900758;
RA Rooney R.J., Daniels R.R., Jenkins N.A., Gilbert D.J., Rothammer K.,
RA Morris S.W., Higgs D.R., Copeland N.G.;
RT "Chromosomal location and tissue expression of the gene encoding the
RT adenovirus E1A-regulated transcription factor E4F in humans and mice.";
RL Mamm. Genome 9:320-323(1998).
RN [7]
RP FUNCTION.
RX PubMed=9418893; DOI=10.1128/mcb.18.1.459;
RA Fernandes E.R., Zhang J.Y., Rooney R.J.;
RT "Adenovirus E1A-regulated transcription factor p120E4F inhibits cell growth
RT and induces the stabilization of the cdk inhibitor p21WAF1.";
RL Mol. Cell. Biol. 18:459-467(1998).
RN [8]
RP OLIGOMERIZATION, PHOSPHORYLATION, DNA-BINDING, AND MUTAGENESIS OF CYS-194;
RP CYS-197; HIS-210; ARG-237; HIS-238; LYS-249 AND CYS-250.
RX PubMed=9512539; DOI=10.1093/nar/26.7.1681;
RA Rooney R.J., Rothammer K., Fernandes E.R.;
RT "Mutational analysis of p50E4F suggests that DNA binding activity is
RT mediated through an alternative structure in a zinc finger domain that is
RT regulated by phosphorylation.";
RL Nucleic Acids Res. 26:1681-1688(1998).
RN [9]
RP FUNCTION.
RX PubMed=10373523; DOI=10.1128/mcb.19.7.4739;
RA Fernandes E.R., Rooney R.J.;
RT "Suppression of E1A-mediated transformation by the p50E4F transcription
RT factor.";
RL Mol. Cell. Biol. 19:4739-4749(1999).
RN [10]
RP FUNCTION, AND INTERACTION WITH TP53.
RX PubMed=10644996; DOI=10.1038/sj.onc.1203250;
RA Sandy P., Gostissa M., Fogal V., Cecco L.D., Szalay K., Rooney R.J.,
RA Schneider C., Del Sal G.;
RT "p53 is involved in the p120E4F-mediated growth arrest.";
RL Oncogene 19:188-199(2000).
RN [11]
RP FUNCTION, REGULATION BY RB1, AND INTERACTION WITH RB1.
RX PubMed=10869426; DOI=10.1073/pnas.130198397;
RA Fajas L., Paul C., Zugasti O., Le Cam L., Polanowska J., Fabbrizio E.,
RA Medema R., Vignais M.-L., Sardet C.;
RT "pRB binds to and modulates the transrepressing activity of the E1A-
RT regulated transcription factor p120E4F.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7738-7743(2000).
RN [12]
RP FUNCTION.
RX PubMed=11283272; DOI=10.1128/mcb.21.8.2956-2966.2001;
RA Fajas L., Paul C., Vie A., Estrach S., Medema R., Blanchard J.M.,
RA Sardet C., Vignais M.-L.;
RT "Cyclin A is a mediator of p120E4F-dependent cell cycle arrest in G1.";
RL Mol. Cell. Biol. 21:2956-2966(2001).
RN [13]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH CDKN2A AND TP53, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12446718; DOI=10.1074/jbc.m210978200;
RA Rizos H., Diefenbach E., Badhwar P., Woodruff S., Becker T.M., Rooney R.J.,
RA Kefford R.F.;
RT "Association of p14ARF with the p120E4F transcriptional repressor enhances
RT cell cycle inhibition.";
RL J. Biol. Chem. 278:4981-4989(2003).
RN [14]
RP INTERACTION WITH HMGA2.
RX PubMed=14645522; DOI=10.1128/mcb.23.24.9104-9116.2003;
RA Tessari M.A., Gostissa M., Altamura S., Sgarra R., Rustighi A.,
RA Salvagno C., Caretti G., Imbriano C., Mantovani R., Del Sal G.,
RA Giancotti V., Manfioletti G.;
RT "Transcriptional activation of the cyclin A gene by the architectural
RT transcription factor HMGA2.";
RL Mol. Cell. Biol. 23:9104-9116(2003).
RN [15]
RP INTERACTION WITH HDAC1.
RX PubMed=12730668; DOI=10.1038/sj.onc.1206379;
RA Colombo R., Draetta G.F., Chiocca S.;
RT "Modulation of p120E4F transcriptional activity by the Gam1 adenoviral
RT early protein.";
RL Oncogene 22:2541-2547(2003).
RN [16]
RP INDUCTION BY ESTROGEN.
RX PubMed=15579445; DOI=10.1016/s0002-9440(10)63253-1;
RA Nakamura Y., Igarashi K., Suzuki T., Kanno J., Inoue T., Tazawa C.,
RA Saruta M., Ando T., Moriyama N., Furukawa T., Ono M., Moriya T., Ito K.,
RA Saito H., Ishibashi T., Takahashi S., Yamada S., Sasano H.;
RT "E4F1, a novel estrogen-responsive gene in possible atheroprotection,
RT revealed by microarray analysis.";
RL Am. J. Pathol. 165:2019-2031(2004).
RN [17]
RP INTERACTION WITH RASSF1.
RX PubMed=14729613; DOI=10.1158/0008-5472.can-03-2622;
RA Fenton S.L., Dallol A., Agathanggelou A., Hesson L., Ahmed-Choudhury J.,
RA Baksh S., Sardet C., Dammann R., Minna J.D., Downward J., Maher E.R.,
RA Latif F.;
RT "Identification of the E1A-regulated transcription factor p120 E4F as an
RT interacting partner of the RASSF1A candidate tumor suppressor gene.";
RL Cancer Res. 64:102-107(2004).
RN [18]
RP FUNCTION.
RX PubMed=15805267; DOI=10.1158/0008-5472.can-04-3593;
RA Ahmed-Choudhury J., Agathanggelou A., Fenton S.L., Ricketts C., Clark G.J.,
RA Maher E.R., Latif F.;
RT "Transcriptional regulation of cyclin A2 by RASSF1A through the enhanced
RT binding of p120E4F to the cyclin A2 promoter.";
RL Cancer Res. 65:2690-2697(2005).
RN [19]
RP SUMOYLATION.
RX PubMed=15876874; DOI=10.4161/cc.4.4.1597;
RA Rizos H., Woodruff S., Kefford R.F.;
RT "p14ARF interacts with the SUMO-conjugating enzyme Ubc9 and promotes the
RT sumoylation of its binding partners.";
RL Cell Cycle 4:597-603(2005).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH TP53.
RX PubMed=17110336; DOI=10.1016/j.cell.2006.09.031;
RA Le Cam L., Linares L.K., Paul C., Julien E., Lacroix M., Hatchi E.,
RA Triboulet R., Bossis G., Shmueli A., Rodriguez M.S., Coux O., Sardet C.;
RT "E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions
RT independently of degradation.";
RL Cell 127:775-788(2006).
RN [21]
RP FUNCTION, INTERACTION WITH BMI1, AND SUBCELLULAR LOCATION.
RX PubMed=16882984; DOI=10.1101/gad.1453406;
RA Chagraoui J., Niessen S.L., Lessard J., Girard S., Coulombe P.,
RA Sauvageau M., Meloche S., Sauvageau G.;
RT "E4F1: a novel candidate factor for mediating BMI1 function in primitive
RT hematopoietic cells.";
RL Genes Dev. 20:2110-2120(2006).
RN [22]
RP FUNCTION, AND INTERACTION WITH FHL2.
RX PubMed=16652157; DOI=10.1038/sj.onc.1209567;
RA Paul C., Lacroix M., Iankova I., Julien E., Schaefer B.W., Labalette C.,
RA Wei Y., Le Cam A., Le Cam L., Sardet C.;
RT "The LIM-only protein FHL2 is a negative regulator of E4F1.";
RL Oncogene 25:5475-5484(2006).
RN [23]
RP INTERACTION WITH HBV PROTEIN X (MICROBIAL INFECTION).
RX PubMed=16112766; DOI=10.1016/j.virusres.2005.07.003;
RA Rui E., Moura P.R., Goncalves K.A., Rooney R.J., Kobarg J.;
RT "Interaction of the hepatitis B virus protein HBx with the human
RT transcription regulatory protein p120E4F in vitro.";
RL Virus Res. 115:31-42(2006).
RN [24]
RP INTERACTION WITH ANP32A.
RX PubMed=17557114; DOI=10.1038/sj.embor.7400983;
RA Cvetanovic M., Rooney R.J., Garcia J.J., Toporovskaya N., Zoghbi H.Y.,
RA Opal P.;
RT "The role of LANP and ataxin 1 in E4F-mediated transcriptional
RT repression.";
RL EMBO Rep. 8:671-677(2007).
RN [25]
RP IDENTIFICATION BY 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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50, 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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
CC -!- FUNCTION: May function as a transcriptional repressor. May also
CC function as a ubiquitin ligase mediating ubiquitination of chromatin-
CC associated TP53. Functions in cell survival and proliferation through
CC control of the cell cycle. Functions in the p53 and pRB tumor
CC suppressor pathways and regulates the cyclin CCNA2 transcription.
CC -!- FUNCTION: Identified as a cellular target of the adenoviral oncoprotein
CC E1A, it is required for both transcriptional activation and repression
CC of viral genes.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:17110336};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer; binds DNA as a dimer. Forms a complex with CDKN2A
CC and TP53. Interactions with TP53, RB1, ANP32A, BMI1 and FHL2 regulate
CC E4F1 activity. Interacts with HDAC1, HMGA2 and RASSF1.
CC {ECO:0000269|PubMed:10644996, ECO:0000269|PubMed:10869426,
CC ECO:0000269|PubMed:12446718, ECO:0000269|PubMed:12730668,
CC ECO:0000269|PubMed:14645522, ECO:0000269|PubMed:14729613,
CC ECO:0000269|PubMed:16652157, ECO:0000269|PubMed:16882984,
CC ECO:0000269|PubMed:17110336, ECO:0000269|PubMed:17557114}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HBV protein X.
CC {ECO:0000269|PubMed:16112766}.
CC -!- INTERACTION:
CC Q66K89; P39687: ANP32A; NbExp=3; IntAct=EBI-1227043, EBI-359234;
CC Q66K89; Q13547: HDAC1; NbExp=3; IntAct=EBI-1227043, EBI-301834;
CC Q66K89; Q6IT96: HDAC1; NbExp=2; IntAct=EBI-1227043, EBI-6979193;
CC Q66K89; Q9NS23-2: RASSF1; NbExp=7; IntAct=EBI-1227043, EBI-438698;
CC Q66K89; Q64770: 8; Xeno; NbExp=4; IntAct=EBI-1227043, EBI-8642971;
CC Q66K89; A4VCF7: lnx2b; Xeno; NbExp=3; IntAct=EBI-1227043, EBI-6979266;
CC Q66K89; Q9YHE8: tcf7l1a; Xeno; NbExp=2; IntAct=EBI-1227043, EBI-6979298;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Cytoplasm. Note=A small
CC fraction is detected in the cytoplasm. Excluded from the nucleolus
CC where it is targeted upon CDKN2A overexpression. Localizes to the
CC mitotic spindle during embryogenesis. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:9530632}.
CC -!- DEVELOPMENTAL STAGE: Expressed in a variety of fetal tissues.
CC {ECO:0000269|PubMed:9530632}.
CC -!- INDUCTION: Up-regulated by estrogen. {ECO:0000269|PubMed:15579445}.
CC -!- PTM: Proteolytic cleavage produces a 50 kDa N-terminal peptide (p50E4F)
CC which has a DNA-binding activity and activates transcription in
CC presence of the adenoviral E1A protein. The major full-length protein
CC (p120E4F) functions as a repressor of transcription.
CC {ECO:0000269|PubMed:9121437}.
CC -!- PTM: Phosphorylated; p120E4F and p50E4F are both phosphorylated.
CC Phosphorylation is cell cycle-dependent and differentially regulates
CC DNA-binding activity and function of both forms.
CC {ECO:0000269|PubMed:9121437, ECO:0000269|PubMed:9512539}.
CC -!- PTM: May be sumoylated by UBE2I upon interaction with CDKN2A.
CC {ECO:0000269|PubMed:15876874}.
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DR EMBL; U87269; AAD09139.1; -; mRNA.
DR EMBL; AK290329; BAF83018.1; -; mRNA.
DR EMBL; AC009065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85532.1; -; Genomic_DNA.
DR EMBL; BC080524; AAH80524.1; -; mRNA.
DR CCDS; CCDS32370.1; -.
DR RefSeq; NP_001275705.1; NM_001288776.1.
DR RefSeq; NP_001275707.1; NM_001288778.1.
DR RefSeq; NP_004415.3; NM_004424.4.
DR AlphaFoldDB; Q66K89; -.
DR SMR; Q66K89; -.
DR BioGRID; 108209; 97.
DR IntAct; Q66K89; 75.
DR MINT; Q66K89; -.
DR STRING; 9606.ENSP00000301727; -.
DR iPTMnet; Q66K89; -.
DR PhosphoSitePlus; Q66K89; -.
DR BioMuta; E4F1; -.
DR DMDM; 296434488; -.
DR EPD; Q66K89; -.
DR jPOST; Q66K89; -.
DR MassIVE; Q66K89; -.
DR MaxQB; Q66K89; -.
DR PaxDb; Q66K89; -.
DR PeptideAtlas; Q66K89; -.
DR PRIDE; Q66K89; -.
DR ProteomicsDB; 65963; -.
DR Antibodypedia; 23652; 112 antibodies from 18 providers.
DR DNASU; 1877; -.
DR Ensembl; ENST00000301727.9; ENSP00000301727.4; ENSG00000167967.16.
DR GeneID; 1877; -.
DR KEGG; hsa:1877; -.
DR MANE-Select; ENST00000301727.9; ENSP00000301727.4; NM_004424.5; NP_004415.4.
DR UCSC; uc002cpm.5; human.
DR CTD; 1877; -.
DR DisGeNET; 1877; -.
DR GeneCards; E4F1; -.
DR HGNC; HGNC:3121; E4F1.
DR HPA; ENSG00000167967; Low tissue specificity.
DR MIM; 603022; gene.
DR neXtProt; NX_Q66K89; -.
DR OpenTargets; ENSG00000167967; -.
DR PharmGKB; PA27579; -.
DR VEuPathDB; HostDB:ENSG00000167967; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00840000129970; -.
DR InParanoid; Q66K89; -.
DR OMA; MGNQIMK; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q66K89; -.
DR TreeFam; TF315387; -.
DR PathwayCommons; Q66K89; -.
DR SignaLink; Q66K89; -.
DR SIGNOR; Q66K89; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 1877; 431 hits in 1109 CRISPR screens.
DR ChiTaRS; E4F1; human.
DR GeneWiki; E4F1; -.
DR GenomeRNAi; 1877; -.
DR Pharos; Q66K89; Tbio.
DR PRO; PR:Q66K89; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q66K89; protein.
DR Bgee; ENSG00000167967; Expressed in right hemisphere of cerebellum and 93 other tissues.
DR ExpressionAtlas; Q66K89; baseline and differential.
DR Genevisible; Q66K89; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005819; C:spindle; IEA:Ensembl.
DR GO; GO:0035497; F:cAMP response element binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:UniProtKB.
DR GO; GO:0010564; P:regulation of cell cycle process; IDA:UniProtKB.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0009794; P:regulation of mitotic cell cycle, embryonic; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 5.
DR SMART; SM00355; ZnF_C2H2; 10.
DR SUPFAM; SSF57667; SSF57667; 5.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 7.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 9.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cytoplasm; DNA-binding; Growth regulation;
KW Host-virus interaction; Metal-binding; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..784
FT /note="Transcription factor E4F1"
FT /id="PRO_0000324307"
FT ZN_FING 192..214
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 220..242
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 248..272
FT /note="C2H2-type 3; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 435..457
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 463..485
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 491..513
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 519..541
FT /note="C2H2-type 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 547..569
FT /note="C2H2-type 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 575..597
FT /note="C2H2-type 9; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 41..85
FT /note="Required for ubiquitin ligase activity"
FT REGION 184..263
FT /note="Mediates dimerization, DNA-binding, transcription
FT repression of CCNA2 and interaction with HMGA2"
FT /evidence="ECO:0000269|PubMed:14645522"
FT REGION 369..566
FT /note="Mediates interaction with CDKN2A"
FT REGION 435..599
FT /note="Interaction with BMI1"
FT /evidence="ECO:0000269|PubMed:16882984"
FT REGION 521..580
FT /note="Mediates interaction with TP53"
FT REGION 575..597
FT /note="Mediates interaction with RASSF1"
FT /evidence="ECO:0000269|PubMed:14729613"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231"
FT VARIANT 167
FT /note="R -> H (in dbSNP:rs26839)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9121437,
FT ECO:0000269|Ref.4"
FT /id="VAR_060270"
FT VARIANT 355
FT /note="V -> I (in dbSNP:rs59784157)"
FT /id="VAR_060271"
FT MUTAGEN 194
FT /note="C->S: Increases DNA-binding; when associated with S-
FT 197."
FT /evidence="ECO:0000269|PubMed:9512539"
FT MUTAGEN 197
FT /note="C->S: Increases DNA-binding; when associated with S-
FT 194."
FT /evidence="ECO:0000269|PubMed:9512539"
FT MUTAGEN 210
FT /note="H->A: Alters DNA-binding."
FT /evidence="ECO:0000269|PubMed:9512539"
FT MUTAGEN 237
FT /note="R->L: Alters DNA-binding; when associated with N-
FT 238."
FT /evidence="ECO:0000269|PubMed:9512539"
FT MUTAGEN 238
FT /note="H->N: Alters DNA-binding; when associated with L-
FT 237."
FT /evidence="ECO:0000269|PubMed:9512539"
FT MUTAGEN 249
FT /note="K->M: Alters DNA-binding; when associated with S-
FT 250."
FT /evidence="ECO:0000269|PubMed:9512539"
FT MUTAGEN 250
FT /note="C->S: Alters DNA-binding; when associated with M-
FT 249."
FT /evidence="ECO:0000269|PubMed:9512539"
FT CONFLICT 4
FT /note="A -> E (in Ref. 1; AAD09139)"
FT /evidence="ECO:0000305"
FT CONFLICT 363..364
FT /note="SE -> RK (in Ref. 1; AAD09139)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="A -> V (in Ref. 2; BAF83018)"
FT /evidence="ECO:0000305"
FT CONFLICT 480..481
FT /note="KH -> TD (in Ref. 1; AAD09139)"
FT /evidence="ECO:0000305"
FT CONFLICT 544
FT /note="E -> D (in Ref. 2; BAF83018)"
FT /evidence="ECO:0000305"
FT CONFLICT 681..682
FT /note="QA -> PR (in Ref. 1; AAD09139)"
FT /evidence="ECO:0000305"
FT CONFLICT 704..705
FT /note="EA -> RG (in Ref. 1; AAD09139)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 784 AA; 83496 MW; 60F6E711F2748FD8 CRC64;
MEGAMAVRVT AAHTAEAQAE AGREAGEGAV AAVAAALAPS GFLGLPAPFS EEDEDDVHRC
GRCQAEFTAL EDFVQHKIQK ACQRAPPEAL PATPATTALL GQEVVPAAPG PEEPITVAHI
VVEAASLAAD ISHASDLVGG GHIKEVIVAA EAELGDGEMA EAPGSPRQQG LGLAGEGEQA
QVKLLVNKDG RYVCALCHKT FKTGSILKAH MVTHSSRKDH ECKLCGASFR TKGSLIRHHR
RHTDERPYKC SKCGKSFRES GALTRHLKSL TPCTEKIRFS VSKDVVVSKE DARAGSGAGA
AGLGTATSSV TGEPIETSPV IHLVTDAKGT VIHEVHVQMQ ELSLGMKALA PEPPVSQELP
CSSEGSRENL LHQAMQNSGI VLERAAGEEG ALEPAPAAGS SPQPLAVAAP QLPVLEVQPL
ETQVASEASA VPRTHPCPQC SETFPTAATL EAHKRGHTGP RPFACAQCGK AFPKAYLLKK
HQEVHVRERR FRCGDCGKLY KTIAHVRGHR RVHSDERPYP CPKCGKRYKT KNAQQVHFRT
HLEEKPHVCQ FCSRGFREKG SLVRHVRHHT GEKPFKCYKC GRGFAEHGTL NRHLRTKGGC
LLEVEELLVS EDSPAAATTV LTEDPHTVLV EFSSVVADTQ EYIIEATADD AETSEATEII
EGTQTEVDSH IMKVVQQIVH QASAGHQIIV QNVTMDEETA LGPEAAAADT ITIATPESLT
EQVAMTLASA ISEGTVLAAR AGTSGTEQAT VTMVSSEDIE ILEHAGELVI ASPEGQLEVQ
TVIV
