Protein: Transcription factor E2F8 (E2F-8) (Q58FA4)
Organism: Mus musculus (Mouse)
Function: Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene.
Subcellular location: Nucleus {ECO:0000269|PubMed:15722552}.
Sequence: MENQKENLFSEPHKRGLMKSPLHPSSKANMVLAEIQPDLGPLTTPTKPKEVSQGEPWTPTANLKMLISAVSPEIRSRDQKRGLSDNRSALPEARDCLHEHLSGDEFEKSQPSRKEKSLGLLCHKFLARYPKYPNPAVNNDICLDEVAEELNVERRRIYDIVNVLESLHMVSRLAKNRYTWHGRHNLTKTLGTLKSVGEENKYAEQIMMIKRKEYEQEFDFIKSCGIEDHVIKSHTGQNGHSDMCFVELPGVEFRAASVNSRKDKSLRVMSQKFVMLFLVSTPQIVSLEIAAKILIGEDHVEDLDKSKYKTKIRRLYDIANVLSSLDLIKKVHVTEERGRKPAFKWTGPEISPNNSGSSPIMPLPASLEAEQSAKENCAKNLFSTRGKPSFTRHPSLIKLVKSIENDRRKISSAPSSPVKSNKAESSQNSPPVPNKMAQLAAICKMQLEEQSSEPRKKVKVNLARSGHYKPLAPLDPTVNTELELLTPSLIQPLGVVPLIPSPLSSAVPVILPQAPSGPSYAIYLQPAQAQMLTPPPGLSPTVCPTQPSNATGSKDPTDAPAEKTATDAATTGSLQPAPERHGAKHRSKETTGDRGTKRMITAEDSGPSSVKKPKEDLKALENVPTPTPLFPSGYLIPLTQCSSLGPDSVLSNTENSGTPSPNHRIYGSPIAGVIPVASSELTAVNFPPFHVTPLKLMVSPTSMAAVPVGNSPALNSGHPAPAQNPSSAIVNFTLQHLGLISPGVQMSASPGPGAGTVPVSPRVEADNLSSRQRRATNHDSPVLGQSQLNGQPVAGTGAQQPVPVTPKGSQLVAENFFRTPGGPTKPTSSPYTDFDGANKTSFGTLFVPQRKLEVSTEDIH
InterPro domains: - IPR036390: Winged helix DNA-binding domain superfamily (homologous_superfamily) [115-348]
- IPR015633: E2F Family (family) [41-450]
- IPR003316: E2F/DP family, winged-helix DNA-binding domain (domain) [113-347]
- IPR036388: Winged helix-like DNA-binding domain superfamily (homologous_superfamily) [108-348]
Interaction partners: - Transcription factor E2F7
- Cyclin-A2
- Kinesin-like protein KIF11
- Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
- Cell division control protein 6 homolog
- DNA topoisomerase 2-alpha
- Disks large-associated protein 5
- Proliferation marker protein Ki-67
- Transcription factor Dp-2
- Transcription factor E2F6
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0140110 (transcription regulator activity), GO:1901363 (heterocyclic compound binding), GO:0003700 (DNA-binding transcription factor activity), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0001217 (DNA-binding transcription repressor activity), GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0001227 (DNA-binding transcription repressor activity, RNA polymerase II-specific), GO:0001067 (transcription regulatory region nucleic acid binding), GO:0003677 (DNA binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0000976 (transcription cis-regulatory region binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0000987 (cis-regulatory region sequence-specific DNA binding), GO:0000977 (RNA polymerase II transcription regulatory region sequence-specific DNA binding), GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0022414 (reproductive process), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0009653 (anatomical structure morphogenesis), GO:0019222 (regulation of metabolic process), GO:0003006 (developmental process involved in reproduction), GO:0048646 (anatomical structure formation involved in morphogenesis), GO:0009892 (negative regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0048523 (negative regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0051302 (regulation of cell division), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0090068 (positive regulation of cell cycle process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0001568 (blood vessel development), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0008285 (negative regulation of cell population proliferation), GO:0060706 (cell differentiation involved in embryonic placenta development), GO:0048513 (animal organ development), GO:0060255 (regulation of macromolecule metabolic process), GO:0051782 (negative regulation of cell division), GO:0010948 (negative regulation of cell cycle process), GO:0031324 (negative regulation of cellular metabolic process), GO:0045787 (positive regulation of cell cycle), GO:0001525 (angiogenesis), GO:0035295 (tube development), GO:0051726 (regulation of cell cycle), GO:0042127 (regulation of cell population proliferation), GO:0009888 (tissue development), GO:0031325 (positive regulation of cellular metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0045786 (negative regulation of cell cycle), GO:0009890 (negative regulation of biosynthetic process), GO:0009790 (embryo development), GO:0080090 (regulation of primary metabolic process), GO:0010564 (regulation of cell cycle process), GO:0035239 (tube morphogenesis), GO:1901988 (negative regulation of cell cycle phase transition), GO:0007346 (regulation of mitotic cell cycle), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051052 (regulation of DNA metabolic process), GO:0051054 (positive regulation of DNA metabolic process), GO:0001944 (vasculature development), GO:0048732 (gland development), GO:0032875 (regulation of DNA endoreduplication), GO:0032465 (regulation of cytokinesis), GO:0061008 (hepaticobiliary system development), GO:0001890 (placenta development), GO:0010468 (regulation of gene expression), GO:0030855 (epithelial cell differentiation), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0048568 (embryonic organ development), GO:0048514 (blood vessel morphogenesis), GO:0032466 (negative regulation of cytokinesis), GO:0072359 (circulatory system development), GO:1901987 (regulation of cell cycle phase transition), GO:0045930 (negative regulation of mitotic cell cycle), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0060429 (epithelium development), GO:0051253 (negative regulation of RNA metabolic process), GO:0002040 (sprouting angiogenesis), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0009792 (embryo development ending in birth or egg hatching), GO:0043009 (chordate embryonic development), GO:1901991 (negative regulation of mitotic cell cycle phase transition), GO:0001892 (embryonic placenta development), GO:0045740 (positive regulation of DNA replication), GO:2001141 (regulation of RNA biosynthetic process), GO:0070365 (hepatocyte differentiation), GO:0006355 (regulation of DNA-templated transcription), GO:1901990 (regulation of mitotic cell cycle phase transition), GO:0001889 (liver development), GO:0006275 (regulation of DNA replication), GO:1902806 (regulation of cell cycle G1/S phase transition), GO:1902807 (negative regulation of cell cycle G1/S phase transition), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0001701 (in utero embryonic development), GO:2000134 (negative regulation of G1/S transition of mitotic cell cycle), GO:0045892 (negative regulation of DNA-templated transcription), GO:0090329 (regulation of DNA-templated DNA replication), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:2000105 (positive regulation of DNA-templated DNA replication), GO:2000045 (regulation of G1/S transition of mitotic cell cycle), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)