E2F1_MOUSE
ID E2F1_MOUSE Reviewed; 430 AA.
AC Q61501; Q80VZ3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Transcription factor E2F1 {ECO:0000303|PubMed:8114719};
DE Short=E2F-1 {ECO:0000303|PubMed:8114719};
GN Name=E2f1 {ECO:0000303|PubMed:8114719, ECO:0000312|MGI:MGI:101941};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Swiss albino;
RX PubMed=8114719; DOI=10.1128/mcb.14.3.1861-1869.1994;
RA Li Y., Slansky J.E., Myers D.J., Drinkwater N.R., Kaelin W.G. Jr.,
RA Farnham P.J.;
RT "Cloning, chromosomal location, and characterization of mouse E2F1.";
RL Mol. Cell. Biol. 14:1861-1869(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP 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 [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=9376316; DOI=10.1016/s0925-4773(97)00083-x;
RA Dagnino L., Fry C.J., Bartley S.M., Farnham P., Gallie B.L., Phillips R.A.;
RT "Expression patterns of the E2F family of transcription factors during
RT mouse nervous system development.";
RL Mech. Dev. 66:13-25(1997).
RN [5]
RP FUNCTION IN APOPTOSIS.
RX PubMed=9674698; DOI=10.1038/sj.onc.1201915;
RA Holmberg C., Helin K., Sehested M., Karlstroem O.;
RT "E2F-1-induced p53-independent apoptosis in transgenic mice.";
RL Oncogene 17:143-155(1998).
RN [6]
RP FUNCTION.
RX PubMed=11672531; DOI=10.1016/s0092-8674(01)00516-5;
RA Porse B.T., Pedersen T.A., Xu X., Lindberg B., Wewer U.M., Friis-Hansen L.,
RA Nerlov C.;
RT "E2F repression by C/EBPalpha is required for adipogenesis and
RT granulopoiesis in vivo.";
RL Cell 107:247-258(2001).
RN [7]
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 [8]
RP INTERACTION WITH RB1.
RX PubMed=20940255; DOI=10.1242/jcs.068924;
RA Pickard A., Wong P.P., McCance D.J.;
RT "Acetylation of Rb by PCAF is required for nuclear localization and
RT keratinocyte differentiation.";
RL J. Cell Sci. 123:3718-3726(2010).
RN [9]
RP FUNCTION.
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).
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:11672531,
CC PubMed:20176812, PubMed:9674698). The DRTF1/E2F complex functions in
CC the control of cell-cycle progression from G1 to S phase (By
CC similarity). E2F1 binds preferentially RB1 in a cell-cycle dependent
CC manner (By similarity). It can mediate both cell proliferation and
CC TP53/p53-dependent apoptosis (PubMed:9674698). Blocks adipocyte
CC differentiation by binding to specific promoters repressing CEBPA
CC binding to its target gene promoters (PubMed:11672531,
CC PubMed:20176812). Directly activates transcription of PEG10 (By
CC similarity). Positively regulates transcription of RRP1B (By
CC similarity). {ECO:0000250|UniProtKB:Q01094,
CC ECO:0000269|PubMed:11672531, ECO:0000269|PubMed:20176812,
CC ECO:0000269|PubMed:9674698}.
CC -!- ACTIVITY REGULATION: BIRC2/c-IAP1 stimulates its transcriptional
CC activity. {ECO:0000250|UniProtKB:Q01094}.
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. Interacts with TRRAP, which probably
CC mediates its interaction with histone acetyltransferase complexes,
CC leading to transcription activation. Binds TOPBP1 and EAPP. Interacts
CC with ARID3A. Interacts with TRIM28; the interaction inhibits E2F1
CC acetylation through recruiting HDAC1 and represses its transcriptional
CC activity. Interaction with KAT2B; the interaction acetylates E2F1
CC enhancing its DNA-binding and transcriptional activity. Interacts with
CC BIRC2/c-IAP1 (via BIR domains). The complex TFDP1:E2F1 interacts with
CC CEBPA; the interaction prevents CEBPA binding to target genes promoters
CC and represses its transcriptional activity. Interacts with RRP1B (By
CC similarity). Interacts with HCFC1 (By similarity). Interacts with
CC KMT2E; the interaction is probably indirect and is mediated via HCFC1
CC (By similarity). {ECO:0000250|UniProtKB:Q01094,
CC ECO:0000269|PubMed:15716352, ECO:0000269|PubMed:8336704}.
CC -!- INTERACTION:
CC Q61501; P25233: Ndn; NbExp=6; IntAct=EBI-1025536, EBI-1801080;
CC Q61501; Q9CPR8: Nsmce3; NbExp=5; IntAct=EBI-1025536, EBI-5529102;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q01094}.
CC -!- DEVELOPMENTAL STAGE: In the developing nervous system, first detected
CC in the neural tube at 9.5 dpc. By 10.5 dpc, levels increase throughout
CC the brain, with highest levels in the hindbrain and in the spinal cord,
CC expressed only in the rostral half. By 11.5 dpc, expression found
CC throughout the brain and spinal cord. From 12.5 dpc, expression
CC restricted to the ventricular regions of the brain, peaks at 13.5 dpc
CC and declines thereafter. Only weak expression in the developing spinal
CC cord from 11.5-16.5 dpc. In the developing retina, expression is
CC confined to the undifferentiated retinoblastic cell layer. In other
CC developing tissues, E2F1 is expressed in kidney, lung, liver
CC hepatocytes, heart and thymus. Highest levels in liver. Absent in
CC choroid plexus. {ECO:0000269|PubMed:9376316}.
CC -!- PTM: Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase.
CC Phosphorylation by CHEK2 stabilizes E2F1 upon DNA damage and regulates
CC its effect on transcription and apoptosis. Phosphorylation at Ser-396
CC by GSK3B promotes interaction with USP11, leading to its
CC deubiquitination and stabilization. {ECO:0000250|UniProtKB:Q01094}.
CC -!- PTM: Ubiquitinated via 'Lys-63'-linked ubiquitin, leading to its
CC degradation. Deubiquitinated by USP11 follwong phosphorylation by
CC GSK3B, promoting its stability. {ECO:0000250|UniProtKB:Q01094}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q01094}.
CC -!- SIMILARITY: Belongs to the E2F/DP family. {ECO:0000305}.
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DR EMBL; L21973; AAA83217.1; -; mRNA.
DR EMBL; BC052160; AAH52160.2; -; mRNA.
DR CCDS; CCDS16935.1; -.
DR PIR; A56209; A56209.
DR RefSeq; NP_031917.1; NM_007891.5.
DR AlphaFoldDB; Q61501; -.
DR SMR; Q61501; -.
DR BioGRID; 199350; 21.
DR ComplexPortal; CPX-159; E2F1-DP1 transcription factor complex.
DR ComplexPortal; CPX-160; RB1-E2F1-TFDP1 transcription repressor complex.
DR CORUM; Q61501; -.
DR IntAct; Q61501; 7.
DR MINT; Q61501; -.
DR STRING; 10090.ENSMUSP00000099434; -.
DR iPTMnet; Q61501; -.
DR PhosphoSitePlus; Q61501; -.
DR PaxDb; Q61501; -.
DR PRIDE; Q61501; -.
DR ProteomicsDB; 277664; -.
DR Antibodypedia; 3771; 1454 antibodies from 48 providers.
DR DNASU; 13555; -.
DR Ensembl; ENSMUST00000103145; ENSMUSP00000099434; ENSMUSG00000027490.
DR GeneID; 13555; -.
DR KEGG; mmu:13555; -.
DR UCSC; uc008njk.2; mouse.
DR CTD; 1869; -.
DR MGI; MGI:101941; E2f1.
DR VEuPathDB; HostDB:ENSMUSG00000027490; -.
DR eggNOG; KOG2577; Eukaryota.
DR GeneTree; ENSGT00940000159472; -.
DR HOGENOM; CLU_032091_0_1_1; -.
DR InParanoid; Q61501; -.
DR OMA; HVCTTQL; -.
DR OrthoDB; 1087250at2759; -.
DR PhylomeDB; Q61501; -.
DR TreeFam; TF105566; -.
DR Reactome; R-MMU-68911; G2 Phase.
DR Reactome; R-MMU-69231; Cyclin D associated events in G1.
DR BioGRID-ORCS; 13555; 3 hits in 75 CRISPR screens.
DR ChiTaRS; E2f1; mouse.
DR PRO; PR:Q61501; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q61501; protein.
DR Bgee; ENSMUSG00000027490; Expressed in animal zygote and 216 other tissues.
DR ExpressionAtlas; Q61501; baseline and differential.
DR Genevisible; Q61501; MM.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0000228; C:nuclear chromosome; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0035189; C:Rb-E2F complex; ISO:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
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:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:MGI.
DR GO; GO:0043276; P:anoikis; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
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; IDA:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:MGI.
DR GO; GO:1990086; P:lens fiber cell apoptotic process; IDA:MGI.
DR GO; GO:0048255; P:mRNA stabilization; ISO:MGI.
DR GO; GO:0043392; P:negative regulation of DNA binding; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0070345; P:negative regulation of fat cell proliferation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0071930; P:negative regulation of transcription involved in G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:MGI.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB.
DR CDD; cd14660; E2F_DD; 1.
DR Gene3D; 1.10.10.10; -; 1.
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 Acetylation; Activator; Apoptosis; Cell cycle; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..430
FT /note="Transcription factor E2F1"
FT /id="PRO_0000219462"
FT DNA_BIND 105..189
FT /evidence="ECO:0000255"
FT REGION 62..103
FT /note="Cyclin A:CDK2 binding"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT REGION 84..186
FT /note="Interaction with BIRC2/c-IAP1"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT REGION 95..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 148..169
FT /note="Leucine-zipper"
FT REGION 187..375
FT /note="Required for interaction with TRIM28"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT REGION 190..279
FT /note="Dimerization"
FT /evidence="ECO:0000255"
FT REGION 294..340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 361..430
FT /note="Transactivation"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT REGION 402..419
FT /note="RB1 binding"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT MOTIF 153..189
FT /note="DEF box"
FT COMPBIAS 302..318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 112
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT MOD_RES 115
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT MOD_RES 120
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT MOD_RES 396
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
FT MOD_RES 426
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q01094"
SQ SEQUENCE 430 AA; 46323 MW; C5DF18AD3B4DFEFA CRC64;
MAVAPAGGQH APALEALLGA GALRLLDSSQ IVIISTAPDV GAPQLPAAPP TGPRDSDVLL
FATPQAPRPA PSAPRPALGR PPVKRRLDLE TDHQYLAGSS GPFRGRGRHP GKGVKSPGEK
SRYETSLNLT TKRFLELLSR SADGVVDLNW AAEVLKVQKR RIYDITNVLE GIQLIAKKSK
NHIQWLGSHT MVGIGKRLEG LTQDLQQLQE SEQQLDHLMH ICTTQLQLLS EDSDTQRLAY
VTCQDLRSIA DPAEQMVIVI KAPPETQLQA VDSSETFQIS LKSKQGPIDV FLCPEESADG
ISPGKTSCQE TSSGEDRTAD SGPAGPPPSP PSTSPALDPS QSLLGLEQEA VLPRMGHLRV
PMEEDQLSPL VAADSLLEHV KEDFSGLLPG EFISLSPPHE ALDYHFGLEE GEGIRDLFDC
DFGDLTPLDF
