ID   E2F4_MOUSE              Reviewed;         410 AA.
AC   Q8R0K9; Q8R2X6;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   27-MAR-2024, entry version 178.
DE   RecName: Full=Transcription factor E2F4;
DE            Short=E2F-4;
GN   Name=E2f4;
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 [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Liver, and Spleen;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II, and FVB/N; TISSUE=Colon, and Mammary tumor;
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   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=17383628; DOI=10.1016/j.ydbio.2007.02.037;
RA   Danielian P.S., Bender Kim C.F., Caron A.M., Vasile E., Bronson R.T.,
RA   Lees J.A.;
RT   "E2f4 is required for normal development of the airway epithelium.";
RL   Dev. Biol. 305:564-576(2007).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-381, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Kidney, Lung, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(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. The DRTF1/E2F complex
CC       functions in the control of cell-cycle progression from G1 to S phase.
CC       E2F4 binds with high affinity to RBL1 and RBL2. In some instances can
CC       also bind RB1. Specifically required for multiciliate cell
CC       differentiation: together with MCIDAS and E2F5, binds and activate
CC       genes required for centriole biogenesis. {ECO:0000250|UniProtKB:Q16254,
CC       ECO:0000250|UniProtKB:Q6DE14, ECO:0000269|PubMed:17383628}.
CC   -!- SUBUNIT: Component of the DRTF1/E2F transcription factor complex. Binds
CC       cooperatively with TFDP1/Dp-1 to E2F sites. The E2F4/TFDP1 dimer
CC       interacts preferentially with pocket protein RBL1, which inhibits the
CC       E2F transactivation domain. Lower affinity interaction has been found
CC       with retinoblastoma protein RB1. Interacts with TRRAP, which probably
CC       mediates its interaction with histone acetyltransferase complexes,
CC       leading to transcription activation. Interacts with HCFC1. Component of
CC       the DREAM complex (also named LINC complex) at least composed of E2F4,
CC       E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1
CC       and TFDP2. The complex exists in quiescent cells where it represses
CC       cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37,
CC       LIN52 and LIN54 form a subcomplex that binds to MYBL2. Interacts with
CC       PML. Interacts with CEBPA (when phosphorylated) (By similarity).
CC       {ECO:0000250|UniProtKB:Q16254}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q16254}.
CC   -!- PTM: Differentially phosphorylated in vivo. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Postnatal lethality, probably due to the absence
CC       of ciliated cells from the entire airway epithelium and the epithelium
CC       of the submucosal glands in the paranasal sinuses. In the nasal
CC       epithelium, ciliated cells are replaced by columnar secretory cells
CC       that produce mucin-like substances. In the proximal lung, reduction in
CC       club cells is also observed. The combination of no ciliated cells and
CC       excess mucous cells leads for the chronic rhinitis and increased
CC       susceptibility to opportunistic infections that cause lethality.
CC       {ECO:0000269|PubMed:17383628}.
CC   -!- SIMILARITY: Belongs to the E2F/DP family. {ECO:0000305}.
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DR   EMBL; AK145950; BAE26778.1; -; mRNA.
DR   EMBL; AK157028; BAE33937.1; -; mRNA.
DR   EMBL; BC023859; AAH23859.1; -; mRNA.
DR   EMBL; BC026649; AAH26649.1; -; mRNA.
DR   EMBL; BC027048; AAH27048.1; -; mRNA.
DR   CCDS; CCDS40456.1; -.
DR   RefSeq; NP_683754.1; NM_148952.1.
DR   AlphaFoldDB; Q8R0K9; -.
DR   SMR; Q8R0K9; -.
DR   BioGRID; 222608; 4.
DR   CORUM; Q8R0K9; -.
DR   IntAct; Q8R0K9; 10.
DR   MINT; Q8R0K9; -.
DR   STRING; 10090.ENSMUSP00000015003; -.
DR   iPTMnet; Q8R0K9; -.
DR   PhosphoSitePlus; Q8R0K9; -.
DR   EPD; Q8R0K9; -.
DR   MaxQB; Q8R0K9; -.
DR   PaxDb; 10090-ENSMUSP00000015003; -.
DR   PeptideAtlas; Q8R0K9; -.
DR   ProteomicsDB; 275424; -.
DR   Pumba; Q8R0K9; -.
DR   Antibodypedia; 4294; 523 antibodies from 41 providers.
DR   DNASU; 104394; -.
DR   Ensembl; ENSMUST00000015003.10; ENSMUSP00000015003.9; ENSMUSG00000014859.10.
DR   GeneID; 104394; -.
DR   KEGG; mmu:104394; -.
DR   UCSC; uc009ncl.1; mouse.
DR   AGR; MGI:103012; -.
DR   CTD; 1874; -.
DR   MGI; MGI:103012; E2f4.
DR   VEuPathDB; HostDB:ENSMUSG00000014859; -.
DR   eggNOG; KOG2577; Eukaryota.
DR   GeneTree; ENSGT00940000156252; -.
DR   HOGENOM; CLU_032091_2_2_1; -.
DR   InParanoid; Q8R0K9; -.
DR   OMA; VQNSPHT; -.
DR   OrthoDB; 1761at2759; -.
DR   PhylomeDB; Q8R0K9; -.
DR   TreeFam; TF105566; -.
DR   Reactome; R-MMU-1538133; G0 and Early G1.
DR   Reactome; R-MMU-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR   Reactome; R-MMU-69231; Cyclin D associated events in G1.
DR   BioGRID-ORCS; 104394; 9 hits in 82 CRISPR screens.
DR   ChiTaRS; E2f4; mouse.
DR   PRO; PR:Q8R0K9; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; Q8R0K9; Protein.
DR   Bgee; ENSMUSG00000014859; Expressed in embryonic post-anal tail and 162 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IBA:GO_Central.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0001216; F:DNA-binding transcription activator activity; ISO:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
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; IBA:GO_Central.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; ISO:MGI.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR   GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR   GO; GO:0008015; P:blood circulation; IMP:MGI.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0006884; P:cell volume homeostasis; IMP:MGI.
DR   GO; GO:0098534; P:centriole assembly; ISS:UniProtKB.
DR   GO; GO:0060271; P:cilium assembly; IMP:MGI.
DR   GO; GO:0002064; P:epithelial cell development; IMP:MGI.
DR   GO; GO:0044458; P:motile cilium assembly; ISS:UniProtKB.
DR   GO; GO:1903251; P:multi-ciliated epithelial cell differentiation; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR   GO; GO:0051726; P:regulation of cell cycle; TAS:MGI.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI.
DR   GO; GO:0008361; P:regulation of cell size; IMP:MGI.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; TAS:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR   CDD; cd14660; E2F_DD; 1.
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   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:SF42; TRANSCRIPTION FACTOR E2F4; 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; Q8R0K9; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Activator; Cell cycle; Cilium biogenesis/degradation;
KW   DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW   Transcription regulation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q16254"
FT   CHAIN           2..410
FT                   /note="Transcription factor E2F4"
FT                   /id="PRO_0000322638"
FT   DNA_BIND        16..85
FT                   /evidence="ECO:0000255"
FT   REGION          1..20
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          43..65
FT                   /note="Leucine-zipper"
FT   REGION          86..181
FT                   /note="Dimerization"
FT                   /evidence="ECO:0000255"
FT   REGION          203..258
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          303..341
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          334..410
FT                   /note="Transactivation"
FT                   /evidence="ECO:0000255"
FT   REGION          387..404
FT                   /note="Interaction with RBL1 and RBL2"
FT                   /evidence="ECO:0000255"
FT   MOTIF           48..85
FT                   /note="DEF box"
FT                   /evidence="ECO:0000250"
FT   MOTIF           386..389
FT                   /note="HCFC1-binding-motif (HBM)"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        1..16
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        204..248
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        303..334
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:Q16254"
FT   MOD_RES         381
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   CONFLICT        326
FT                   /note="P -> T (in Ref. 2; AAH27048)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   410 AA;  43833 MW;  A8BD1A24B38C2B01 CRC64;
     MAEAGPQAPP PPGTPSRHEK SLGLLTTKFV SLLQEAKDGV LDLKLAADTL AVRQKRRIYD
     ITNVLEGIGL IEKKSKNSIQ WKGVGPGCNT REIADKLIEL KAEIEELQQR EQELDQHKVW
     VQQSIRNVTE DVQNSCLAYV THEDICRCFA GDTLLAIRAP SGTSLEVPIP EGLNGQKKYQ
     IHLKSMSGPI EVLLVNKEAW SSPPVAVPVP PPDDLLQSPP AVSTPPPLPK PALAQPQESS
     PPSSPQLTTP TPVLGSTQVS EVACQTSEIA VSGSPGTENK DSGEVSSLPL GLTALDTRPL
     QSSALLDSSS SSSSSSSSSS SSSSGPNPST SFEPIKADPT GVLDLPKELS EIFDPTRECM
     SSELLEELMS SEVFAPLLRL SPPPGDHDYI YNLDESEGVC DLFDVPVLKL
//