O75461 (E2F6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor E2F6
Short name=E2F-6

Gene names

Name:

E2F6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	281 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibitor of E2F-dependent transcription. Binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3'. Has a preference for the 5'-TTTCCCGC-3' E2F recognition site. E2F6 lacks the transcriptional activation and pocket protein binding domains. Appears to regulate a subset of E2F-dependent genes whose products are required for entry into the cell cycle but not for normal cell cycle progression. May silence expression via the recruitment of a chromatin remodeling complex containing histone H3-K9 methyltransferase activity. Overexpression delays the exit of cells from the S-phase.
Subunit structure	Component of the DRTF1/E2F transcription factor complex. Forms heterodimers with DP family members. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Component of some MLL1/MLL complex, at least composed of the core components MLL, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Ref.9 Ref.10
Subcellular location	Nucleus.
Tissue specificity	Expressed in all tissues examined. Highest levels in placenta, skeletal muscle, heart, ovary, kidney, small intestine and spleen.
Sequence similarities	Belongs to the E2F/DP family.

Ontologies

Keywords
Biological process	Cell cycle Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of transcription from RNA polymerase II promoter Traceable author statement Ref.8. Source: ProtInc regulation of transcription involved in G1/S phase of mitotic cell cycle Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	MLL1 complex Inferred from direct assay Ref.10. Source: UniProtKB transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular_function	DNA binding Traceable author statement Ref.8. Source: ProtInc sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara transcription corepressor activity Traceable author statement Ref.8. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75461-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O75461-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 281	281	Transcription factor E2F6		PRO_0000219472
Regions
	DNA binding	50 – 129	80	Potential
	Region	130 – 222	93	Dimerization Potential
	Region	143 – 164	22	Leucine-zipper
	Region	173 – 281	109	Transcription repression
	Motif	95 – 129	35	DEF box
	Compositional bias	265 – 268	4	Poly-Glu
Amino acid modifications
	Modified residue	67	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 75	75	Missing in isoform 2.		VSP_008771
Experimental info
	Mutagenesis	68	1	L → E: Reduction in repressor activity, little effect on S-phase entry.
	Sequence conflict	7 – 8	2	AR → HE in AAC14694. Ref.8
	Sequence conflict	220	1	I → V in AAC14694. Ref.8
	Sequence conflict	229	1	G → E in AAC14694. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 539E049C15AD3508	FASTA	281	31,844
	10 20 30 40 50 60 MSQQRPARKL PSLLLDPTEE TVRRRCRDPI NVEGLLPSKI RINLEDNVQY VSMRKALKVK 70 80 90 100 110 120 RPRFDVSLVY LTRKFMDLVR SAPGGILDLN KVATKLGVRK RRVYDITNVL DGIDLVEKKS 130 140 150 160 170 180 KNHIRWIGSD LSNFGAVPQQ KKLQEELSDL SAMEDALDEL IKDCAQQLFE LTDDKENERL 190 200 210 220 230 240 AYVTYQDIHS IQAFHEQIVI AVKAPAETRL DVPAPREDSI TVHIRSTNGP IDVYLCEVEQ 250 260 270 280 GQTSNKRSEG VGTSSSESTH PEGPEEEENP QQSEELLEVS N
	Isoform 2 [UniParc]. Checksum: 6C79669AFD6F42EC	FASTA	206	22,982
	10 20 30 40 50 60 MDLVRSAPGG ILDLNKVATK LGVRKRRVYD ITNVLDGIDL VEKKSKNHIR WIGSDLSNFG 70 80 90 100 110 120 AVPQQKKLQE ELSDLSAMED ALDELIKDCA QQLFELTDDK ENERLAYVTY QDIHSIQAFH 130 140 150 160 170 180 EQIVIAVKAP AETRLDVPAP REDSITVHIR STNGPIDVYL CEVEQGQTSN KRSEGVGTSS 190 200 SESTHPEGPE EEENPQQSEE LLEVSN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6." Gaubatz S., Wood J.G., Livingston D.M. Proc. Natl. Acad. Sci. U.S.A. 95:9190-9195(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription." Cartwright P., Mueller H., Wagener C., Holm K., Helin K. Oncogene 17:611-623(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[3]	"Sequence for human E2F-6 alternative transcript." Salih M., Tuana B.S. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2). Tissue: Heart.
[4]	"Cloning, genomic organisation and chromosomal mapping of the human E2F6/EMA gene." Schwertfeger N., Taudien S., Truss M., Morkel M., Pohlers M., Gruska I., Haaf T., Rosenthal A., Hagemeier C. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Umbilical cord blood.
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 1). Tissue: Lung.
[8]	"E2F-6, a member of the E2F family that can behave as a transcriptional repressor." Trimarchi J.M., Fairchild B., Verona R., Moberg K., Andon N., Lees J.A. Proc. Natl. Acad. Sci. U.S.A. 95:2850-2855(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-281 (ISOFORM 1). Tissue: Fetal brain.
[9]	"A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells." Ogawa H., Ishiguro K., Gaubatz S., Livingston D.M., Nakatani Y. Science 296:1132-1136(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH TFDP1; MAX; MGA; EUHMTASE1; BAT8; CBX3; RING1; RNF2; MBLR; L3MBTL2 AND YAF2.
[10]	"Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF." Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J., Allis C.D., Chait B.T., Hess J.L., Roeder R.G. Cell 121:873-885(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE MLL1/MLL COMPLEX.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF059292 mRNA. Translation: AAC31426.1. AY083996 mRNA. Translation: AAM10783.1. AY083997 Genomic DNA. Translation: AAM10784.1. AY083997 Genomic DNA. Translation: AAM10785.1. AJ493061 Genomic DNA. Translation: CAD37950.1. AK290413 mRNA. Translation: BAF83102.1. AC099344 Genomic DNA. Translation: AAY14826.1. BC008348 mRNA. Translation: AAH08348.1. BC107740 mRNA. Translation: AAI07741.1. AF041381 mRNA. Translation: AAC14694.1.
IPI	IPI00289560. IPI01011061.
RefSeq	NP_937987.2. NM_198256.2.
UniGene	Hs.603093.
3D structure databases
ProteinModelPortal	O75461.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-41699N.
IntAct	O75461. 4 interactions.
MINT	MINT-158232.
STRING	9606.ENSP00000370936.
PTM databases
PhosphoSite	O75461.
Proteomic databases
PaxDb	O75461.
PRIDE	O75461.
Protocols and materials databases
DNASU	1876.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000381525; ENSP00000370936; ENSG00000169016. ENST00000542100; ENSP00000446315; ENSG00000169016. ENST00000546212; ENSP00000438864; ENSG00000169016.
GeneID	1876.
KEGG	hsa:1876.
UCSC	uc002rbe.3. human.
Organism-specific databases
CTD	1876.
GeneCards	GC02M011584.
H-InvDB	HIX0060106.
HGNC	HGNC:3120. E2F6.
MIM	602944. gene.
neXtProt	NX_O75461.
PharmGKB	PA27578.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG251536.
HOGENOM	HOG000112309.
HOVERGEN	HBG002227.
InParanoid	O75461.
KO	K09390.
OMA	INLEENV.
OrthoDB	EOG4R23VP.
Enzyme and pathway databases
SignaLink	O75461.
Gene expression databases
ArrayExpress	O75461.
Bgee	O75461.
CleanEx	HS_E2F6.
Genevestigator	O75461.
GermOnline	ENSG00000169016. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR015633. E2F. IPR003316. E2F_TDP. IPR015635. Transcription_factor_E2F6. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
PANTHER	PTHR12081. PTHR12081. 1 hit. PTHR12081:SF19. PTHR12081:SF19. 1 hit.
Pfam	PF02319. E2F_TDP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1876.
NextBio	7671.
SOURCE	Search...

Entry information

Entry name

E2F6_HUMAN

Accession

Primary (citable) accession number: O75461
Secondary accession number(s): A8K2Z8 , O60544, Q53QY9, Q7Z2H6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1998
Last modified:	May 29, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.