E2F4_MOUSE
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 03-AUG-2022, entry version 169.
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 Clara cell is also obrserved. 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; Q8R0K9; -.
DR PeptideAtlas; Q8R0K9; -.
DR PRIDE; Q8R0K9; -.
DR ProteomicsDB; 275424; -.
DR Antibodypedia; 4294; 464 antibodies from 41 providers.
DR DNASU; 104394; -.
DR Ensembl; ENSMUST00000015003; ENSMUSP00000015003; ENSMUSG00000014859.
DR GeneID; 104394; -.
DR KEGG; mmu:104394; -.
DR UCSC; uc009ncl.1; mouse.
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; 1087250at2759; -.
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 77 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 159 other tissues.
DR Genevisible; Q8R0K9; MM.
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: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: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:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:MGI.
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; IPR028312; E2F4.
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 PANTHER; PTHR12081:SF42; PTHR12081:SF42; 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; 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
