E2F2_HUMAN
ID E2F2_HUMAN Reviewed; 437 AA.
AC Q14209; B2R9W1; Q7Z6H1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Transcription factor E2F2;
DE Short=E2F-2;
GN Name=E2F2;
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].
RC TISSUE=Cervix carcinoma;
RX PubMed=8246995; DOI=10.1128/mcb.13.12.7802-7812.1993;
RA Ivey-Hoyle M., Conroy R., Huber H.E., Goodhart P.J., Oliff A.,
RA Heimbrook D.C.;
RT "Cloning and characterization of E2F-2, a novel protein with the
RT biochemical properties of transcription factor E2F.";
RL Mol. Cell. Biol. 13:7802-7812(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [GENOMIC DNA], AND VARIANTS ARG-205 AND HIS-226.
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-226.
RC TISSUE=Eye;
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 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 [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 X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 410-427 IN COMPLEX WITH RB.
RX PubMed=12502741; DOI=10.1101/gad.1046102;
RA Lee C., Chang J.H., Lee H.S., Cho Y.;
RT "Structural basis for the recognition of the E2F transactivation domain by
RT the retinoblastoma tumor suppressor.";
RL Genes Dev. 16:3199-3212(2002).
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 E2F2 binds specifically to RB1 in a cell-cycle dependent manner.
CC -!- SUBUNIT: Component of the DRTF1/E2F transcription factor complex. Forms
CC heterodimers with DP family members. The E2F2 complex binds
CC specifically hypophosphorylated retinoblastoma protein RB1. During the
CC cell cycle, RB1 becomes phosphorylated in mid-to-late G1 phase,
CC detaches from the DRTF1/E2F complex, rendering E2F transcriptionally
CC active. Viral oncoproteins, notably E1A, T-antigen and HPV E7, are
CC capable of sequestering RB1, thus releasing the active complex. Binds
CC EAPP. {ECO:0000269|PubMed:12502741}.
CC -!- INTERACTION:
CC Q14209; P06400: RB1; NbExp=5; IntAct=EBI-718476, EBI-491274;
CC Q14209; Q14186: TFDP1; NbExp=3; IntAct=EBI-718476, EBI-749713;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Highest level of expression is found in placenta,
CC low levels are found in lung. Found as well in many immortalized cell
CC lines derived from tumor samples.
CC -!- PTM: Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the E2F/DP family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/e2f2/";
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DR EMBL; L22846; AAA16890.1; -; mRNA.
DR EMBL; AK313939; BAG36658.1; -; mRNA.
DR EMBL; AF518877; AAM54044.1; -; Genomic_DNA.
DR EMBL; AL021154; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC053676; AAH53676.1; -; mRNA.
DR CCDS; CCDS236.1; -.
DR PIR; A54595; A54595.
DR RefSeq; NP_004082.1; NM_004091.3.
DR PDB; 1N4M; X-ray; 2.20 A; C/D/E=410-427.
DR PDBsum; 1N4M; -.
DR AlphaFoldDB; Q14209; -.
DR SMR; Q14209; -.
DR BioGRID; 108202; 35.
DR ComplexPortal; CPX-175; RB1-E2F2-TFDP1 transcription repressor complex.
DR ComplexPortal; CPX-1972; E2F2-DP1 transcription factor complex.
DR DIP; DIP-258N; -.
DR ELM; Q14209; -.
DR IntAct; Q14209; 13.
DR MINT; Q14209; -.
DR STRING; 9606.ENSP00000355249; -.
DR ChEMBL; CHEMBL4630726; -.
DR iPTMnet; Q14209; -.
DR PhosphoSitePlus; Q14209; -.
DR BioMuta; E2F2; -.
DR DMDM; 2494228; -.
DR MassIVE; Q14209; -.
DR MaxQB; Q14209; -.
DR PaxDb; Q14209; -.
DR PeptideAtlas; Q14209; -.
DR PRIDE; Q14209; -.
DR ProteomicsDB; 59931; -.
DR Antibodypedia; 4274; 350 antibodies from 36 providers.
DR DNASU; 1870; -.
DR Ensembl; ENST00000361729.3; ENSP00000355249.2; ENSG00000007968.7.
DR Ensembl; ENST00000634683.2; ENSP00000489612.1; ENSG00000282899.2.
DR GeneID; 1870; -.
DR KEGG; hsa:1870; -.
DR MANE-Select; ENST00000361729.3; ENSP00000355249.2; NM_004091.4; NP_004082.1.
DR UCSC; uc001bhe.3; human.
DR CTD; 1870; -.
DR DisGeNET; 1870; -.
DR GeneCards; E2F2; -.
DR HGNC; HGNC:3114; E2F2.
DR HPA; ENSG00000007968; Group enriched (bone marrow, esophagus, lymphoid tissue).
DR MIM; 600426; gene.
DR neXtProt; NX_Q14209; -.
DR OpenTargets; ENSG00000007968; -.
DR PharmGKB; PA27572; -.
DR VEuPathDB; HostDB:ENSG00000007968; -.
DR eggNOG; KOG2577; Eukaryota.
DR GeneTree; ENSGT00940000160992; -.
DR HOGENOM; CLU_032091_0_0_1; -.
DR InParanoid; Q14209; -.
DR OMA; WVGRGIF; -.
DR OrthoDB; 1087250at2759; -.
DR PhylomeDB; Q14209; -.
DR TreeFam; TF105566; -.
DR PathwayCommons; Q14209; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2559585; Oncogene Induced Senescence.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-9661069; Defective binding of RB1 mutants to E2F1,(E2F2, E2F3).
DR SignaLink; Q14209; -.
DR SIGNOR; Q14209; -.
DR BioGRID-ORCS; 1870; 13 hits in 1109 CRISPR screens.
DR EvolutionaryTrace; Q14209; -.
DR GeneWiki; E2F2; -.
DR GenomeRNAi; 1870; -.
DR Pharos; Q14209; Tbio.
DR PRO; PR:Q14209; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q14209; protein.
DR Bgee; ENSG00000007968; Expressed in bone marrow and 77 other tissues.
DR Genevisible; Q14209; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:NTNU_SB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IEA:Ensembl.
DR GO; GO:1990086; P:lens fiber cell apoptotic process; IEA:Ensembl.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; IGI:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:ProtInc.
DR CDD; cd14660; E2F_DD; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR IDEAL; IID00171; -.
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; Activator; Cell cycle; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..437
FT /note="Transcription factor E2F2"
FT /id="PRO_0000219464"
FT DNA_BIND 107..196
FT /evidence="ECO:0000255"
FT REGION 65..105
FT /note="Cyclin A/CDK2 binding"
FT /evidence="ECO:0000255"
FT REGION 155..176
FT /note="Leucine-zipper"
FT REGION 197..289
FT /note="Dimerization"
FT /evidence="ECO:0000255"
FT REGION 307..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 359..437
FT /note="Transactivation"
FT /evidence="ECO:0000255"
FT REGION 410..427
FT /note="Retinoblastoma protein binding"
FT /evidence="ECO:0000255"
FT MOTIF 160..196
FT /note="DEF box"
FT COMPBIAS 314..344
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..367
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 205
FT /note="G -> R (in dbSNP:rs2229297)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018990"
FT VARIANT 226
FT /note="Q -> H (in dbSNP:rs2075995)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_018991"
FT HELIX 422..424
FT /evidence="ECO:0007829|PDB:1N4M"
SQ SEQUENCE 437 AA; 47506 MW; 60541F4235507005 CRC64;
MLQGPRALAS AAGQTPKVVP AMSPTELWPS GLSSPQLCPA TATYYTPLYP QTAPPAAAPG
TCLDATPHGP EGQVVRCLPA GRLPAKRKLD LEGIGRPVVP EFPTPKGKCI RVDGLPSPKT
PKSPGEKTRY DTSLGLLTKK FIYLLSESED GVLDLNWAAE VLDVQKRRIY DITNVLEGIQ
LIRKKAKNNI QWVGRGMFED PTRPGKQQQL GQELKELMNT EQALDQLIQS CSLSFKHLTE
DKANKRLAYV TYQDIRAVGN FKEQTVIAVK APPQTRLEVP DRTEDNLQIY LKSTQGPIEV
YLCPEEVQEP DSPSEEPLPS TSTLCPSPDS AQPSSSTDPS IMEPTASSVP APAPTPQQAP
PPPSLVPLEA TDSLLELPHP LLQQTEDQFL SPTLACSSPL ISFSPSLDQD DYLWGLEAGE
GISDLFDSYD LGDLLIN
