UniProtKB - A0AVK6 (E2F8_HUMAN)
Protein
Transcription factor E2F8
Gene
E2F8
Organism
Homo sapiens (Human)
Status
Functioni
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.4 Publications
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 113 – 182 | Sequence analysisAdd BLAST | 70 | |
DNA bindingi | 261 – 347 | Sequence analysisAdd BLAST | 87 |
GO - Molecular functioni
- cis-regulatory region sequence-specific DNA binding Source: UniProtKB
- DNA binding Source: GO_Central
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription repressor activity Source: UniProtKB
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: NTNU_SB
- identical protein binding Source: Ensembl
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: NTNU_SB
- sequence-specific DNA binding Source: GO_Central
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- transcription factor binding Source: GO_Central
GO - Biological processi
- cell cycle comprising mitosis without cytokinesis Source: UniProtKB
- cell population proliferation Source: Ensembl
- chorionic trophoblast cell differentiation Source: UniProtKB
- DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
- hepatocyte differentiation Source: UniProtKB
- negative regulation of cytokinesis Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: NTNU_SB
- placenta development Source: UniProtKB
- positive regulation of DNA endoreduplication Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of cell cycle Source: GO_Central
- sprouting angiogenesis Source: UniProtKB
- trophoblast giant cell differentiation Source: UniProtKB
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Cell cycle, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | A0AVK6 |
Reactomei | R-HSA-6804116, TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest |
Names & Taxonomyi
Protein namesi | Recommended name: Transcription factor E2F8Short name: E2F-8 |
Gene namesi | Name:E2F8 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:24727, E2F8 |
MIMi | 612047, gene |
neXtProti | NX_A0AVK6 |
VEuPathDBi | HostDB:ENSG00000129173.12 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Cytosol
- cytosol Source: HPA
Nucleus
- nuclear chromatin Source: NTNU_SB
- nucleolus Source: HPA
- nucleoplasm Source: HPA
- nucleus Source: GO_Central
Other locations
- RNA polymerase II transcription regulator complex Source: GO_Central
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 156 | R → A: Loss of DNA-binding and inhibition of E2F1-dependent activation. Impairs DNA-binding and dimerization; when associated with A-314. 2 Publications | 1 | |
Mutagenesisi | 314 | R → A: Loss of DNA-binding and inhibition of E2F1-dependent activation. Impairs DNA-binding and dimerization; when associated with A-156. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 79733 |
OpenTargetsi | ENSG00000129173 |
PharmGKBi | PA142671918 |
Miscellaneous databases
Pharosi | A0AVK6, Tbio |
Genetic variation databases
BioMutai | E2F8 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000298909 | 1 – 867 | Transcription factor E2F8Add BLAST | 867 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 71 | PhosphoserineCombined sources | 1 | |
Modified residuei | 102 | PhosphoserineCombined sources | 1 | |
Modified residuei | 413 | PhosphoserineCombined sources | 1 | |
Modified residuei | 417 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | A0AVK6 |
jPOSTi | A0AVK6 |
MassIVEi | A0AVK6 |
MaxQBi | A0AVK6 |
PaxDbi | A0AVK6 |
PeptideAtlasi | A0AVK6 |
PRIDEi | A0AVK6 |
ProteomicsDBi | 24 |
PTM databases
iPTMneti | A0AVK6 |
PhosphoSitePlusi | A0AVK6 |
Expressioni
Inductioni
Following DNA damage (PubMed:18202719). Up-regulation in response to DNA damage is not confirmed by PubMed:22802528.1 Publication
Gene expression databases
Bgeei | ENSG00000129173, Expressed in biceps brachii and 145 other tissues |
ExpressionAtlasi | A0AVK6, baseline and differential |
Genevisiblei | A0AVK6, HS |
Organism-specific databases
HPAi | ENSG00000129173, Tissue enhanced (lymphoid) |
Interactioni
Subunit structurei
Homodimer and heterodimer: mainly forms homodimers and, to a lesser extent, heterodimers with E2F8. Dimerization is important for DNA-binding.
Interacts with HIF1A.
3 PublicationsBinary interactionsi
Hide detailsA0AVK6
GO - Molecular functioni
- identical protein binding Source: Ensembl
- transcription factor binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 122847, 14 interactors |
IntActi | A0AVK6, 23 interactors |
MINTi | A0AVK6 |
STRINGi | 9606.ENSP00000481103 |
Miscellaneous databases
RNActi | A0AVK6, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | A0AVK6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer (By similarity).By similarity
Sequence similaritiesi
Belongs to the E2F/DP family.Curated
Phylogenomic databases
eggNOGi | KOG2578, Eukaryota |
GeneTreei | ENSGT00940000158651 |
HOGENOMi | CLU_014845_2_0_1 |
InParanoidi | A0AVK6 |
OMAi | PNGHPDM |
OrthoDBi | 145070at2759 |
PhylomeDBi | A0AVK6 |
TreeFami | TF105567 |
Family and domain databases
Gene3Di | 1.10.10.10, 2 hits |
InterProi | View protein in InterPro IPR015633, E2F IPR003316, E2F_WHTH_DNA-bd_dom IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR12081, PTHR12081, 1 hit |
Pfami | View protein in Pfam PF02319, E2F_TDP, 2 hits |
SMARTi | View protein in SMART SM01372, E2F_TDP, 2 hits |
SUPFAMi | SSF46785, SSF46785, 2 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
A0AVK6-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MENEKENLFC EPHKRGLMKT PLKESTTANI VLAEIQPDFG PLTTPTKPKE
60 70 80 90 100
GSQGEPWTPT ANLKMLISAV SPEIRNRDQK RGLFDNRSGL PEAKDCIHEH
110 120 130 140 150
LSGDEFEKSQ PSRKEKSLGL LCHKFLARYP NYPNPAVNND ICLDEVAEEL
160 170 180 190 200
NVERRRIYDI VNVLESLHMV SRLAKNRYTW HGRHNLNKTL GTLKSIGEEN
210 220 230 240 250
KYAEQIMMIK KKEYEQEFDF IKSYSIEDHI IKSNTGPNGH PDMCFVELPG
260 270 280 290 300
VEFRAASVNS RKDKSLRVMS QKFVMLFLVS TPQIVSLEVA AKILIGEDHV
310 320 330 340 350
EDLDKSKFKT KIRRLYDIAN VLSSLDLIKK VHVTEERGRK PAFKWTGPEI
360 370 380 390 400
SPNTSGSSPV IHFTPSDLEV RRSSKENCAK NLFSTRGKPN FTRHPSLIKL
410 420 430 440 450
VKSIESDRRK INSAPSSPIK TNKAESSQNS APFPSKMAQL AAICKMQLEE
460 470 480 490 500
QSSESRQKVK VQLARSGPCK PVAPLDPPVN AEMELTAPSL IQPLGMVPLI
510 520 530 540 550
PSPLSSAVPL ILPQAPSGPS YAIYLQPTQA HQSVTPPQGL SPTVCTTHSS
560 570 580 590 600
KATGSKDSTD ATTEKAANDT SKASASTRPG SLLPAPERQG AKSRTREPAG
610 620 630 640 650
ERGSKRASML EDSGSKKKFK EDLKGLENVS ATLFPSGYLI PLTQCSSLGA
660 670 680 690 700
ESILSGKENS SALSPNHRIY SSPIAGVIPV TSSELTAVNF PSFHVTPLKL
710 720 730 740 750
MVSPTSVAAV PVGNSPALAS SHPVPIQNPS SAIVNFTLQH LGLISPNVQL
760 770 780 790 800
SASPGSGIVP VSPRIESVNV APENAGTQQG RATNYDSPVP GQSQPNGQSV
810 820 830 840 850
AVTGAQQPVP VTPKGSQLVA ESFFRTPGGP TKPTSSSCMD FEGANKTSLG
860
TLFVPQRKLE VSTEDVH
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketE9PMT9 | E9PMT9_HUMAN | Transcription factor E2F8 | E2F8 | 139 | Annotation score: |
Sequence cautioni
The sequence AAH28244 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence BAB15605 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 138 | N → I in BAE46901 (Ref. 4) Curated | 1 | |
Sequence conflicti | 460 | K → R in BAB15605 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_034735 | 674 | I → V. Corresponds to variant dbSNP:rs793274EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK026964 mRNA Translation: BAB15605.1 Different initiation. AK292688 mRNA Translation: BAF85377.1 CH471064 Genomic DNA Translation: EAW68354.1 BC028244 mRNA Translation: AAH28244.2 Different initiation. BC090877 mRNA Translation: AAH90877.1 BC108700 mRNA Translation: AAI08701.1 BC126400 mRNA Translation: AAI26401.1 BC126402 mRNA Translation: AAI26403.1 AB231781 mRNA Translation: BAE46901.1 |
CCDSi | CCDS7849.1 |
RefSeqi | NP_001243300.1, NM_001256371.1 NP_001243301.1, NM_001256372.1 NP_078956.2, NM_024680.3 |
Genome annotation databases
Ensembli | ENST00000250024; ENSP00000250024; ENSG00000129173 ENST00000527884; ENSP00000434199; ENSG00000129173 ENST00000620009; ENSP00000481103; ENSG00000129173 |
GeneIDi | 79733 |
KEGGi | hsa:79733 |
UCSCi | uc001mpm.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK026964 mRNA Translation: BAB15605.1 Different initiation. AK292688 mRNA Translation: BAF85377.1 CH471064 Genomic DNA Translation: EAW68354.1 BC028244 mRNA Translation: AAH28244.2 Different initiation. BC090877 mRNA Translation: AAH90877.1 BC108700 mRNA Translation: AAI08701.1 BC126400 mRNA Translation: AAI26401.1 BC126402 mRNA Translation: AAI26403.1 AB231781 mRNA Translation: BAE46901.1 |
CCDSi | CCDS7849.1 |
RefSeqi | NP_001243300.1, NM_001256371.1 NP_001243301.1, NM_001256372.1 NP_078956.2, NM_024680.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4YO2 | X-ray | 3.07 | A | 110-341 | [»] | |
SMRi | A0AVK6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 122847, 14 interactors |
IntActi | A0AVK6, 23 interactors |
MINTi | A0AVK6 |
STRINGi | 9606.ENSP00000481103 |
PTM databases
iPTMneti | A0AVK6 |
PhosphoSitePlusi | A0AVK6 |
Genetic variation databases
BioMutai | E2F8 |
Proteomic databases
EPDi | A0AVK6 |
jPOSTi | A0AVK6 |
MassIVEi | A0AVK6 |
MaxQBi | A0AVK6 |
PaxDbi | A0AVK6 |
PeptideAtlasi | A0AVK6 |
PRIDEi | A0AVK6 |
ProteomicsDBi | 24 |
Protocols and materials databases
Antibodypediai | 25218, 193 antibodies |
DNASUi | 79733 |
Genome annotation databases
Ensembli | ENST00000250024; ENSP00000250024; ENSG00000129173 ENST00000527884; ENSP00000434199; ENSG00000129173 ENST00000620009; ENSP00000481103; ENSG00000129173 |
GeneIDi | 79733 |
KEGGi | hsa:79733 |
UCSCi | uc001mpm.4, human |
Organism-specific databases
CTDi | 79733 |
DisGeNETi | 79733 |
GeneCardsi | E2F8 |
HGNCi | HGNC:24727, E2F8 |
HPAi | ENSG00000129173, Tissue enhanced (lymphoid) |
MIMi | 612047, gene |
neXtProti | NX_A0AVK6 |
OpenTargetsi | ENSG00000129173 |
PharmGKBi | PA142671918 |
VEuPathDBi | HostDB:ENSG00000129173.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2578, Eukaryota |
GeneTreei | ENSGT00940000158651 |
HOGENOMi | CLU_014845_2_0_1 |
InParanoidi | A0AVK6 |
OMAi | PNGHPDM |
OrthoDBi | 145070at2759 |
PhylomeDBi | A0AVK6 |
TreeFami | TF105567 |
Enzyme and pathway databases
PathwayCommonsi | A0AVK6 |
Reactomei | R-HSA-6804116, TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest |
Miscellaneous databases
BioGRID-ORCSi | 79733, 7 hits in 901 CRISPR screens |
ChiTaRSi | E2F8, human |
GenomeRNAii | 79733 |
Pharosi | A0AVK6, Tbio |
PROi | PR:A0AVK6 |
RNActi | A0AVK6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000129173, Expressed in biceps brachii and 145 other tissues |
ExpressionAtlasi | A0AVK6, baseline and differential |
Genevisiblei | A0AVK6, HS |
Family and domain databases
Gene3Di | 1.10.10.10, 2 hits |
InterProi | View protein in InterPro IPR015633, E2F IPR003316, E2F_WHTH_DNA-bd_dom IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR12081, PTHR12081, 1 hit |
Pfami | View protein in Pfam PF02319, E2F_TDP, 2 hits |
SMARTi | View protein in SMART SM01372, E2F_TDP, 2 hits |
SUPFAMi | SSF46785, SSF46785, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | E2F8_HUMAN | |
Accessioni | A0AVK6Primary (citable) accession number: A0AVK6 Secondary accession number(s): A8K9H3 Q9H5M0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 21, 2007 |
Last sequence update: | November 28, 2006 | |
Last modified: | February 10, 2021 | |
This is version 131 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families