Reviewed, UniProtKB/Swiss-Prot O75461 (E2F6_HUMAN)

Names and origin

Protein names

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

Gene names

Name:

E2F6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	281 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. E2F-6 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.
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
Gene Ontology (GO)
Biological process	negative regulation of transcription from RNA polymerase II promoter Ref.7 Traceable author statement. Source: ProtInc
Cellular component	transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular function	transcription corepressor activity Ref.7 Traceable author statement. Source: ProtInc transcription factor activity Inferred from electronic annotation. Source: InterPro
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
	Domain	143 – 164	22	Leucine-zipper
	DNA binding	50 – 129	80	Potential
	Region	130 – 222	93	Dimerization Potential
	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.7
	Sequence conflict	220	1	I → V in AAC14694. Ref.7
	Sequence conflict	229	1	G → E in AAC14694. Ref.7

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		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: 9689056] [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: 9704927] [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]	"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: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[7]	"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: 9501179] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-281 (ISOFORM 1). Tissue: Fetal brain.
[8]	"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: 12004135] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH TFDP1; MAX; MGA; EUHMTASE1; BAT8; CBX3; RING1; RNF2; MBLR; L3MBTL2 AND YAF2.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. AC099344 Genomic DNA. Translation: AAY14826.1. BC008348 mRNA. Translation: AAH08348.1. BC107740 mRNA. Translation: AAI07741.1. AF041381 mRNA. Translation: AAC14694.1.
RefSeq	NP_937987.2.
UniGene	Hs.603093
3D structure databases
HSSP	HSSP built from PDB template 1CF7 based on UniProtKB Q16254.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75461.
PTM databases
PhosphoSite	O75461.
Genome annotation databases
Ensembl	ENSG00000169016. Homo sapiens. [Contig view]
GeneID	1876.
KEGG	hsa:1876.
Organism-specific databases
H-InvDB	HIX0001829.
HGNC	HGNC:3120. E2F6.
MIM	602944. gene.
PharmGKB	PA27578.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	O75461.
Gene expression databases
ArrayExpress	O75461.
CleanEx	HS_E2F6.
GermOnline	ENSG00000169016. Homo sapiens.
Family and domain databases
InterPro	IPR015633. E2F. IPR015635. E2F6. IPR003316. E2F_TDP. IPR011991. Wing_hlx_DNA_bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
PANTHER	PTHR12081. E2F. 1 hit. PTHR12081:SF19. E2F6. 1 hit.
Pfam	PF02319. E2F_TDP. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
LinkHub	O75461.
NextBio	7671.
SOURCE	Search...

Entry information

Entry name

E2F6_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1998
Last modified:	November 25, 2008
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)