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Protein

Transcription factor E2F8

Gene

E2F8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi113 – 18270Sequence analysisAdd
BLAST
DNA bindingi261 – 34787Sequence analysisAdd
BLAST

GO - Molecular functioni

  • core promoter binding Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription corepressor activity Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Cell cycle, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor E2F8
Short name:
E2F-8
Gene namesi
Name:E2F8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:24727. E2F8.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi156 – 1561R → A: Loss of DNA-binding and inhibition of E2F1-dependent activation. Impairs DNA-binding and dimerization; when associated with A-314. 2 Publications
Mutagenesisi314 – 3141R → A: Loss of DNA-binding and inhibition of E2F1-dependent activation. Impairs DNA-binding and dimerization; when associated with A-156. 2 Publications

Organism-specific databases

PharmGKBiPA142671918.

Polymorphism and mutation databases

BioMutaiE2F8.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 867867Transcription factor E2F8PRO_0000298909Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei71 – 711PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiA0AVK6.
MaxQBiA0AVK6.
PaxDbiA0AVK6.
PRIDEiA0AVK6.

PTM databases

iPTMnetiA0AVK6.
PhosphoSiteiA0AVK6.

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

BgeeiA0AVK6.
CleanExiHS_E2F8.
ExpressionAtlasiA0AVK6. baseline and differential.
GenevisibleiA0AVK6. HS.

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 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
E2F7Q96AV84EBI-7779316,EBI-1386765
FHL3Q136433EBI-7779316,EBI-741101
TFCP2Q128003EBI-7779316,EBI-717422

Protein-protein interaction databases

BioGridi122847. 7 interactions.
IntActiA0AVK6. 4 interactions.
MINTiMINT-6541611.
STRINGi9606.ENSP00000250024.

Structurei

Secondary structure

1
867
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi114 – 1163Combined sources
Helixi118 – 12811Combined sources
Beta strandi135 – 1373Combined sources
Helixi142 – 1487Combined sources
Helixi154 – 16613Combined sources
Beta strandi169 – 1746Combined sources
Beta strandi177 – 1793Combined sources
Helixi186 – 19611Combined sources
Helixi199 – 20911Combined sources
Helixi266 – 27611Combined sources
Helixi286 – 29611Combined sources
Beta strandi305 – 3073Combined sources
Helixi308 – 32114Combined sources
Beta strandi324 – 3274Combined sources
Beta strandi332 – 3343Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4YO2X-ray3.07A110-341[»]
ProteinModelPortaliA0AVK6.
SMRiA0AVK6. Positions 112-180.
ModBaseiSearch...
MobiDBiSearch...

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

eggNOGiKOG2578. Eukaryota.
ENOG4111IGY. LUCA.
GeneTreeiENSGT00530000063616.
HOVERGENiHBG063270.
InParanoidiA0AVK6.
KOiK09391.
OMAiLIPLTQC.
OrthoDBiEOG7HHWSG.
PhylomeDBiA0AVK6.
TreeFamiTF105567.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR015633. E2F.
IPR003316. E2F_WHTH_DNA-bd_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR12081. PTHR12081. 5 hits.
PfamiPF02319. E2F_TDP. 2 hits.
[Graphical view]
SMARTiSM01372. E2F_TDP. 2 hits.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 2 hits.

Sequencei

Sequence statusi: Complete.

A0AVK6-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:867
Mass (Da):94,166
Last modified:November 28, 2006 - v1
Checksum:iAADBCFACB888BD93
GO

Sequence cautioni

The sequence AAH28244.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAB15605.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti138 – 1381N → I in BAE46901 (Ref. 4) Curated
Sequence conflicti460 – 4601K → R in BAB15605 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti674 – 6741I → V.
Corresponds to variant rs793274 [ dbSNP | Ensembl ].
VAR_034735

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.
CCDSiCCDS7849.1.
RefSeqiNP_001243300.1. NM_001256371.1.
NP_001243301.1. NM_001256372.1.
NP_078956.2. NM_024680.3.
UniGeneiHs.523526.

Genome annotation databases

EnsembliENST00000250024; ENSP00000250024; ENSG00000129173.
ENST00000527884; ENSP00000434199; ENSG00000129173.
ENST00000620009; ENSP00000481103; ENSG00000129173.
GeneIDi79733.
KEGGihsa:79733.
UCSCiuc001mpm.4. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS7849.1.
RefSeqiNP_001243300.1. NM_001256371.1.
NP_001243301.1. NM_001256372.1.
NP_078956.2. NM_024680.3.
UniGeneiHs.523526.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4YO2X-ray3.07A110-341[»]
ProteinModelPortaliA0AVK6.
SMRiA0AVK6. Positions 112-180.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122847. 7 interactions.
IntActiA0AVK6. 4 interactions.
MINTiMINT-6541611.
STRINGi9606.ENSP00000250024.

PTM databases

iPTMnetiA0AVK6.
PhosphoSiteiA0AVK6.

Polymorphism and mutation databases

BioMutaiE2F8.

Proteomic databases

EPDiA0AVK6.
MaxQBiA0AVK6.
PaxDbiA0AVK6.
PRIDEiA0AVK6.

Protocols and materials databases

DNASUi79733.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250024; ENSP00000250024; ENSG00000129173.
ENST00000527884; ENSP00000434199; ENSG00000129173.
ENST00000620009; ENSP00000481103; ENSG00000129173.
GeneIDi79733.
KEGGihsa:79733.
UCSCiuc001mpm.4. human.

Organism-specific databases

CTDi79733.
GeneCardsiE2F8.
HGNCiHGNC:24727. E2F8.
MIMi612047. gene.
neXtProtiNX_A0AVK6.
PharmGKBiPA142671918.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2578. Eukaryota.
ENOG4111IGY. LUCA.
GeneTreeiENSGT00530000063616.
HOVERGENiHBG063270.
InParanoidiA0AVK6.
KOiK09391.
OMAiLIPLTQC.
OrthoDBiEOG7HHWSG.
PhylomeDBiA0AVK6.
TreeFamiTF105567.

Miscellaneous databases

ChiTaRSiE2F8. human.
GenomeRNAii79733.
PROiA0AVK6.
SOURCEiSearch...

Gene expression databases

BgeeiA0AVK6.
CleanExiHS_E2F8.
ExpressionAtlasiA0AVK6. baseline and differential.
GenevisibleiA0AVK6. HS.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR015633. E2F.
IPR003316. E2F_WHTH_DNA-bd_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR12081. PTHR12081. 5 hits.
PfamiPF02319. E2F_TDP. 2 hits.
[Graphical view]
SMARTiSM01372. E2F_TDP. 2 hits.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 2 hits.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Thymus.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Lung, Mammary gland, Skin and Testis.
  4. "Identification of novel human genes predicted by combining multiple gene finders."
    Totoki Y., Yada T., Sakaki Y., Takeda T.
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-139.
  5. "Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription."
    Christensen J., Cloos P., Toftegaard U., Klinkenberg D., Bracken A.P., Trinh E., Heeran M., Di Stefano L., Helin K.
    Nucleic Acids Res. 33:5458-5470(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "E2F-8: an E2F family member with a similar organization of DNA-binding domains to E2F-7."
    Logan N., Graham A., Zhao X., Fisher R., Maiti B., Leone G., La Thangue N.B.
    Oncogene 24:5000-5004(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-156 AND ARG-314.
  7. "Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development."
    Li J., Ran C., Li E., Gordon F., Comstock G., Siddiqui H., Cleghorn W., Chen H.-Z., Kornacker K., Liu C.-G., Pandit S.K., Khanizadeh M., Weinstein M., Leone G., de Bruin A.
    Dev. Cell 14:62-75(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  8. Cited for: FUNCTION, SUBUNIT, MUTAGENESIS OF ARG-156 AND ARG-314.
  9. "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
    Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
    J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  10. "E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1."
    Weijts B.G., Bakker W.J., Cornelissen P.W., Liang K.H., Schaftenaar F.H., Westendorp B., de Wolf C.A., Paciejewska M., Scheele C.L., Kent L., Leone G., Schulte-Merker S., de Bruin A.
    EMBO J. 31:3871-3884(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HIF1A.
  11. "E2F7, a novel target, is up-regulated by p53 and mediates DNA damage-dependent transcriptional repression."
    Carvajal L.A., Hamard P.J., Tonnessen C., Manfredi J.J.
    Genes Dev. 26:1533-1545(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: LACK OF RESPONSE TO DNA DAMAGE.

Entry informationi

Entry nameiE2F8_HUMAN
AccessioniPrimary (citable) accession number: A0AVK6
Secondary accession number(s): A8K9H3
, Q2VPJ3, Q3C1U6, Q5BKY4, Q8N340, Q9H5M0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 21, 2007
Last sequence update: November 28, 2006
Last modified: June 8, 2016
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.