O75530 (EED_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Polycomb protein EED
Short name=hEED

Alternative name(s):
WD protein associating with integrin cytoplasmic tails 1
Short name=WAIT-1

Gene names

Name:

EED

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	441 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A. Ref.2 Ref.9 Ref.14 Ref.16 Ref.17 Ref.19 Ref.22 Ref.27 Ref.30
Subunit structure	Interacts with MLL By similarity. Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12. Component of the PRC2/EED-EZH1 complex, which includes EED, EZH1, SUZ12, RBBP4 and AEBP2. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with HDAC, HDAC2, histone H1 and YY1. May interact with ITGA4, ITGAE and ITGB7. May interact with the MA protein of HIV-1. Ref.2 Ref.3 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.16 Ref.21 Ref.22 Ref.25 Ref.26 Ref.27
Subcellular location	Nucleus. Chromosome. Note: Transiently colocalizes with XIST at inactive X chromosomes. Ref.2 Ref.3 Ref.12 Ref.15 Ref.17
Tissue specificity	Expressed in brain, colon, heart, kidney, liver, lung, muscle, ovary, peripheral blood leukocytes, pancreas, placenta, prostate, spleen, small intestine, testis, thymus and uterus. Appears to be overexpressed in breast and colon cancer. Ref.1 Ref.2 Ref.3 Ref.8 Ref.20
Developmental stage	Expression peaks at the G1/S phase boundary. Ref.14
Induction	Expression is induced by E2F1, E2F2 and E2F3. Ref.14
Domain	The WD repeat domain mediates recognition of trimethylated histone peptides at the consensus sequence Ala-Arg-Lys-Ser. This is achieved through an aromatic cage encircling the methyllysine, and involving Phe-97, Tyr-148 and Tyr-365. Ref.30
Post-translational modification	Methylated. Binding to histone H1 'Lys-26' promotes mono-, di-, and trimethylation of internal lysines. Ref.24 Ref.30
Sequence similarities	Belongs to the WD repeat ESC family. Contains 7 WD repeats.
Caution	Two variants of the PRC2 complex have been described, termed PRC3 and PRC4. Each of the three complexes may include a different complement of EED isoforms, although the precise sequences of the isoforms in each complex have not been determined. The PRC2 and PRC4 complexes may also methylate 'Lys-26' of histone H1 in addition to 'Lys-27' of histone H3 (Ref.18 and Ref.20), although other studies have demonstrated no methylation of 'Lys-26' of histone H1 by PRC2 (Ref.21).
Sequence caution	The sequence AAC23685.1 differs from that shown. Reason: Erroneous initiation. The sequence AAC68675.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Chromosome Nucleus
Coding sequence diversity	Alternative initiation Alternative splicing
Domain	Repeat WD repeat
Molecular function	Chromatin regulator Repressor
PTM	Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of transcription, DNA-dependent Non-traceable author statement Ref.2. Source: UniProtKB regulation of gene expression by genetic imprinting Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	ESC/E(Z) complex Inferred from direct assay PubMed 20075857PubMed 23104054PubMed 23273982. Source: UniProtKB pronucleus Inferred from electronic annotation. Source: Compara sex chromatin Inferred from electronic annotation. Source: Compara
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara histone methyltransferase activity Inferred from direct assay Ref.16. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-923794,EBI-923794
ASXL1	Q8IXJ9	5	EBI-923794,EBI-1646500
DDB1	Q16531	4	EBI-923794,EBI-350322
DNMT1	P26358	3	EBI-923794,EBI-719459
DNMT3A	Q9Y6K1	2	EBI-923794,EBI-923653
DNMT3B	Q9UBC3	4	EBI-923794,EBI-80125
EZH2	Q15910	7	EBI-923794,EBI-530054
PML-RAR	Q15156	2	EBI-923794,EBI-867256

Alternative products

This entry describes 3 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]

Note: Additional isoforms may be produced by alternative initiation, both from non-canonical start codons upstream of the initiator methionine displayed and from other canonical start codons downstream of that displayed (PubMed:15099518 and PubMed:15684044). The precise sites of translation initiation have not been unambiguously identified.

Isoform 1 (identifier: O75530-1)

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: O75530-2)

The sequence of this isoform differs from the canonical sequence as follows:
     322-322: K → KSGRAILHSHQQCMRDPVSPNLRQHL

Isoform 3 (identifier: O75530-3)

The sequence of this isoform differs from the canonical sequence as follows:
     401-441: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 441

441

Polycomb protein EED

PRO_0000343725

Regions

Repeat

91 – 134

44

WD 1

Repeat

142 – 185

44

WD 2

Repeat

188 – 228

41

WD 3

Repeat

234 – 275

42

WD 4

Repeat

304 – 341

38

WD 5

Repeat

359 – 399

41

WD 6

Repeat

408 – 441

34

WD 7

Region

81 – 441

361

Interaction with EZH2 By similarity

Region

149 – 303

155

Required for interaction with the matrix protein MA of HIV-1

Region

301 – 441

141

Required for interaction with the matrix protein MA of HIV-1

Amino acid modifications

Modified residue

55

1

Phosphothreonine Ref.28

Modified residue

66

1

N6,N6,N6-trimethyllysine; alternate Ref.30

Modified residue

66

1

N6,N6-dimethyllysine; alternate Ref.30

Modified residue

66

1

N6-methyllysine; alternate Ref.30

Modified residue

197

1

N6,N6,N6-trimethyllysine; alternate Ref.30

Modified residue

197

1

N6,N6-dimethyllysine; alternate Ref.30

Modified residue

197

1

N6-methyllysine; alternate Ref.30

Modified residue

268

1

N6,N6,N6-trimethyllysine; alternate Ref.30

Modified residue

268

1

N6,N6-dimethyllysine; alternate Ref.30

Modified residue

268

1

N6-methyllysine; alternate Ref.30

Modified residue

284

1

N6,N6,N6-trimethyllysine; alternate Ref.30

Modified residue

284

1

N6,N6-dimethyllysine; alternate Ref.30

Modified residue

284

1

N6-methyllysine; alternate Ref.30

Natural variations

Alternative sequence

322

1

K → KSGRAILHSHQQCMRDPVSP NLRQHL in isoform 2.

VSP_034691

Alternative sequence

401 – 441

41

Missing in isoform 3.

VSP_034692

Experimental info

Mutagenesis

97

1

F → A: Abolishes binding to H3K27me3. Ref.3 Ref.30

Mutagenesis

148

1

Y → A: Abolishes binding to H3K27me3. Ref.3 Ref.30

Mutagenesis

193

1

I → N: Impairs interaction with EZH2. Ref.2 Ref.3

Mutagenesis

196

1

L → P: Impairs interaction with EZH2. Ref.2 Ref.3

Mutagenesis

300 – 301

2

ST → AA: Impairs interaction with the matrix protein MA of HIV-1. Ref.3

Mutagenesis

305 – 308

4

HRNY → AAAA: Impairs interaction with the matrix protein MA of HIV-1. Ref.3

Mutagenesis

364

1

W → A: Abolishes binding to H3K27me3. Ref.3 Ref.30

Mutagenesis

364

1

W → L: Abolishes binding to H3K27me3. Ref.3 Ref.30

Mutagenesis

365

1

Y → A: Abolishes binding to H3K27me3. Ref.3 Ref.30

Sequence conflict

32

1

D → E in AAC68675. Ref.8

Sequence conflict

74

1

K → S in AAD08714. Ref.3

Sequence conflict

74

1

K → S in AAD08815. Ref.3

Sequence conflict

337

1

E → K in AAD08714. Ref.3

Sequence conflict

337

1

E → K in AAD08815. Ref.3

Sequence conflict

417

1

S → G in BAF84809. Ref.4

Secondary structure

1

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441

Helix Strand Turn

Details...

Beta strand

83 – 89

7

Beta strand

96 – 101

6

Beta strand

111 – 117

7

Beta strand

120 – 126

7

Helix

128 – 130

3

Beta strand

132 – 139

8

Beta strand

147 – 154

8

Turn

156 – 158

3

Beta strand

161 – 167

7

Beta strand

171 – 175

5

Turn

177 – 179

3

Beta strand

182 – 188

7

Beta strand

193 – 198

6

Beta strand

205 – 210

6

Beta strand

215 – 219

5

Turn

220 – 223

4

Beta strand

224 – 229

6

Beta strand

231 – 234

4

Beta strand

239 – 244

6

Beta strand

248 – 255

8

Beta strand

260 – 265

6

Helix

268 – 278

11

Helix

282 – 284

3

Beta strand

292 – 294

3

Beta strand

298 – 301

4

Beta strand

311 – 315

5

Beta strand

318 – 322

5

Beta strand

324 – 335

12

Helix

340 – 342

3

Beta strand

350 – 357

8

Beta strand

374 – 380

7

Beta strand

386 – 390

5

Beta strand

393 – 395

3

Helix

396 – 398

3

Beta strand

400 – 404

5

Beta strand

413 – 418

6

Beta strand

422 – 429

8

Beta strand

432 – 438

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 22, 2008. Version 2. Checksum: D2E0A5BA27C0499A	FASTA	441	50,198
	10 20 30 40 50 60 MSEREVSTAP AGTDMPAAKK QKLSSDENSN PDLSGDENDD AVSIESGTNT ERPDTPTNTP 70 80 90 100 110 120 NAPGRKSWGK GKWKSKKCKY SFKCVNSLKE DHNQPLFGVQ FNWHSKEGDP LVFATVGSNR 130 140 150 160 170 180 VTLYECHSQG EIRLLQSYVD ADADENFYTC AWTYDSNTSH PLLAVAGSRG IIRIINPITM 190 200 210 220 230 240 QCIKHYVGHG NAINELKFHP RDPNLLLSVS KDHALRLWNI QTDTLVAIFG GVEGHRDEVL 250 260 270 280 290 300 SADYDLLGEK IMSCGMDHSL KLWRINSKRM MNAIKESYDY NPNKTNRPFI SQKIHFPDFS 310 320 330 340 350 360 TRDIHRNYVD CVRWLGDLIL SKSCENAIVC WKPGKMEDDI DKIKPSESNV TILGRFDYSQ 370 380 390 400 410 420 CDIWYMRFSM DFWQKMLALG NQVGKLYVWD LEVEDPHKAK CTTLTHHKCG AAIRQTSFSR 430 440 DSSILIAVCD DASIWRWDRL R
	Isoform 2 [UniParc]. Checksum: 614B2E31B2A9D41F	FASTA	466	53,061
	10 20 30 40 50 60 MSEREVSTAP AGTDMPAAKK QKLSSDENSN PDLSGDENDD AVSIESGTNT ERPDTPTNTP 70 80 90 100 110 120 NAPGRKSWGK GKWKSKKCKY SFKCVNSLKE DHNQPLFGVQ FNWHSKEGDP LVFATVGSNR 130 140 150 160 170 180 VTLYECHSQG EIRLLQSYVD ADADENFYTC AWTYDSNTSH PLLAVAGSRG IIRIINPITM 190 200 210 220 230 240 QCIKHYVGHG NAINELKFHP RDPNLLLSVS KDHALRLWNI QTDTLVAIFG GVEGHRDEVL 250 260 270 280 290 300 SADYDLLGEK IMSCGMDHSL KLWRINSKRM MNAIKESYDY NPNKTNRPFI SQKIHFPDFS 310 320 330 340 350 360 TRDIHRNYVD CVRWLGDLIL SKSGRAILHS HQQCMRDPVS PNLRQHLSCE NAIVCWKPGK 370 380 390 400 410 420 MEDDIDKIKP SESNVTILGR FDYSQCDIWY MRFSMDFWQK MLALGNQVGK LYVWDLEVED 430 440 450 460 PHKAKCTTLT HHKCGAAIRQ TSFSRDSSIL IAVCDDASIW RWDRLR
	Isoform 3 [UniParc]. Checksum: 45DD879776FF83D5	FASTA	400	45,524
	10 20 30 40 50 60 MSEREVSTAP AGTDMPAAKK QKLSSDENSN PDLSGDENDD AVSIESGTNT ERPDTPTNTP 70 80 90 100 110 120 NAPGRKSWGK GKWKSKKCKY SFKCVNSLKE DHNQPLFGVQ FNWHSKEGDP LVFATVGSNR 130 140 150 160 170 180 VTLYECHSQG EIRLLQSYVD ADADENFYTC AWTYDSNTSH PLLAVAGSRG IIRIINPITM 190 200 210 220 230 240 QCIKHYVGHG NAINELKFHP RDPNLLLSVS KDHALRLWNI QTDTLVAIFG GVEGHRDEVL 250 260 270 280 290 300 SADYDLLGEK IMSCGMDHSL KLWRINSKRM MNAIKESYDY NPNKTNRPFI SQKIHFPDFS 310 320 330 340 350 360 TRDIHRNYVD CVRWLGDLIL SKSCENAIVC WKPGKMEDDI DKIKPSESNV TILGRFDYSQ 370 380 390 400 CDIWYMRFSM DFWQKMLALG NQVGKLYVWD LEVEDPHKAK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The murine Polycomb-group gene eed and its human orthologue: functional implications of evolutionary conservation." Schumacher A., Lichtarge O., Schwartz S., Magnuson T. Genomics 54:79-88(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes." Sewalt R.G.A.B., van der Vlag J., Gunster M.J., Hamer K.M., den Blaauwen J.L., Satijn D.P.E., Hendrix T., van Driel R., Otte A.P. Mol. Cell. Biol. 18:3586-3595(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH EZH2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ILE-193 AND LEU-196, PUTATIVE ALTERNATIVE INITIATION.
[3]	"HEED, the product of the human homolog of the murine eed gene, binds to the matrix protein of HIV-1." Peytavi R., Hong S.S., Gay B., d'Angeac A.D., Selig L., Benichou S., Benarous R., Boulanger P. J. Biol. Chem. 274:1635-1645(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), INTERACTION WITH THE HIV-1 MA PROTEIN, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF 300-SER-THR-301 AND 305-HIS-TYR-308. Tissue: Spleen.
[4]	"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: Synovium.
[5]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-441 (ISOFORM 1). Tissue: Eye and Lung.
[8]	"The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins." Rietzler M., Bittner M., Kolanus W., Schuster A., Holzmann B. J. Biol. Chem. 273:27459-27466(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-441 (ISOFORM 1), INTERACTION WITH ITGA4; ITGAE AND ITGB7, TISSUE SPECIFICITY.
[9]	"Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation." van der Vlag J., Otte A.P. Nat. Genet. 23:474-478(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EZH2; HDAC1 AND HDAC2.
[10]	"The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos." Satijn D.P.E., Hamer K.M., den Blaauwen J., Otte A.P. Mol. Cell. Biol. 21:1360-1369(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EZH2 AND YY1.
[11]	"Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein." Kuzmichev A., Nishioka K., Erdjument-Bromage H., Tempst P., Reinberg D. Genes Dev. 16:2893-2905(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX WITH EZH2; RBBP4; RBBP7 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[12]	"Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins." Sewalt R.G.A.B., Lachner M., Vargas M., Hamer K.M., den Blaauwen J.L., Hendrix T., Melcher M., Schweizer D., Jenuwein T., Otte A.P. Mol. Cell. Biol. 22:5539-5553(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[13]	"Role of histone H3 lysine 27 methylation in Polycomb-group silencing." Cao R., Wang L., Wang H., Xia L., Erdjument-Bromage H., Tempst P., Jones R.S., Zhang Y. Science 298:1039-1043(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX WITH EZH2; RBBP4; RBBP7 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[14]	"EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer." Bracken A.P., Pasini D., Capra M., Prosperini E., Colli E., Helin K. EMBO J. 22:5323-5335(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE, INDUCTION.
[15]	"Role of histone H3 lysine 27 methylation in X inactivation." Plath K., Fang J., Mlynarczyk-Evans S.K., Cao R., Worringer K.A., Wang H., de la Cruz C.C., Otte A.P., Panning B., Zhang Y. Science 300:131-135(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[16]	"Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity." Pasini D., Bracken A.P., Jensen M.R., Lazzerini Denchi E., Helin K. EMBO J. 23:4061-4071(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EZH2, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[17]	"Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27." Kirmizis A., Bartley S.M., Kuzmichev A., Margueron R., Reinberg D., Green R., Farnham P.J. Genes Dev. 18:1592-1605(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[18]	"Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3." Kuzmichev A., Jenuwein T., Tempst P., Reinberg D. Mol. Cell 14:183-193(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE PRC2 AND PRC3 COMPLEXES INCLUDING EED; EZH2; RBBP4; RBBP7 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 AND PRC3 COMPLEXES, PUTATIVE ALTERNATIVE INITIATION.
[19]	"SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex." Cao R., Zhang Y. Mol. Cell 15:57-67(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF THE PRC2 COMPLEX INCLUDING AEBP2; EED; EZH2; RBBP4 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[20]	"Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation." Kuzmichev A., Margueron R., Vaquero A., Preissner T.S., Scher M., Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P.J., Reinberg D. Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE PRC4 COMPLEX INCLUDING EED; EZH2; RBBP4; RBBP7; SUZ12 AND SIRT1, METHYLTRANSFERASE ACTIVITY OF THE PRC4 COMPLEX, TISSUE SPECIFICITY.
[21]	"Substrate preferences of the EZH2 histone methyltransferase complex." Martin C., Cao R., Zhang Y. J. Biol. Chem. 281:8365-8370(2006) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX, INTERACTION WITH HISTONE H1.
[22]	"The Polycomb group protein EZH2 directly controls DNA methylation." Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F. Nature 439:871-874(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION OF THE PRC2 COMPLEX WITH DNMT1; DNMT3A AND DNMT3B.
[23]	Erratum Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F. Nature 446:824-824(2007)
[24]	"Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer." Schlesinger Y., Straussman R., Keshet I., Farkash S., Hecht M., Zimmerman J., Eden E., Yakhini Z., Ben-Shushan E., Reubinoff B.E., Bergman Y., Simon I., Cedar H. Nat. Genet. 39:232-236(2007) [PubMed] [Europe PMC] [Abstract] Cited for: DE NOVO DNA METHYLATION OF PRC2 TARGET GENES.
[25]	"Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms." Margueron R., Li G., Sarma K., Blais A., Zavadil J., Woodcock C.L., Dynlacht B.D., Reinberg D. Mol. Cell 32:503-518(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE PRC2/EED-EZH1 COMPLEX.
[26]	"Role of hPHF1 in H3K27 methylation and Hox gene silencing." Cao R., Wang H., He J., Erdjument-Bromage H., Tempst P., Zhang Y. Mol. Cell. Biol. 28:1862-1872(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION OF THE PRC2 COMPLEX WITH PHF1, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[27]	"Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo." Sarma K., Margueron R., Ivanov A., Pirrotta V., Reinberg D. Mol. Cell. Biol. 28:2718-2731(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EZH2 AND SUZ12, INTERACTION OF THE PRC2 COMPLEX WITH PHF1, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[28]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-55, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[29]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]	"Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2)." Xu C., Bian C., Yang W., Galka M., Ouyang H., Chen C., Qiu W., Liu H., Jones A.E., MacKenzie F., Pan P., Li S.S., Wang H., Min J. Proc. Natl. Acad. Sci. U.S.A. 107:19266-19271(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 40-441, ALONE AND IN COMPLEX WITH METHYLATED HISTONE PEPTIDES, FUNCTION, DOMAIN WD REPEATS, METHYLATION AT LYS-66; LYS-197; LYS-268 AND LYS-284, MUTAGENESIS OF PHE-97; TYR-148; TRP-364 AND TYR-365.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF080227 mRNA. Translation: AAC95144.1.
AF070418 mRNA. Translation: AAC23685.1. Different initiation.
U90651 mRNA. Translation: AAD08714.1.
AF099032 mRNA. Translation: AAD08815.1.
AK292120 mRNA. Translation: BAF84809.1.
AP003084 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW75129.1.
CH471076 Genomic DNA. Translation: EAW75130.1.
BC047672 mRNA. Translation: AAH47672.1.
BC068995 mRNA. Translation: AAH68995.1.
AF078933 mRNA. Translation: AAC68675.1. Different initiation.

IPI

IPI00171248.
IPI00395515.
IPI00432040.

RefSeq

NP_003788.2. NM_003797.3.
NP_694536.1. NM_152991.2.

UniGene

Hs.503510.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IIW	X-ray	1.80	A	77-441	[»]
3IIY	X-ray	2.65	A	77-441	[»]
3IJ0	X-ray	2.45	A	77-441	[»]
3IJ1	X-ray	2.10	A	77-441	[»]
3IJC	X-ray	1.95	A	77-441	[»]
3JPX	X-ray	2.05	A	40-441	[»]
3JZG	X-ray	2.10	A	40-441	[»]
3JZH	X-ray	2.05	A	40-441	[»]
3JZN	X-ray	2.60	A	76-441	[»]
3K26	X-ray	1.58	A	76-441	[»]
3K27	X-ray	1.76	A	76-441	[»]

ProteinModelPortal

O75530.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-36673N.

IntAct

O75530. 21 interactions.

STRING

9606.ENSP00000263360.

PTM databases

PhosphoSite

O75530.

Proteomic databases

PaxDb

O75530.

PRIDE

O75530.

Protocols and materials databases

DNASU

8726.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263360; ENSP00000263360; ENSG00000074266.
ENST00000327320; ENSP00000315587; ENSG00000074266.
ENST00000351625; ENSP00000338186; ENSG00000074266.

GeneID

8726.

KEGG

hsa:8726.

UCSC

uc001pbp.3. human.
uc001pbr.3. human.

Organism-specific databases

CTD

8726.

GeneCards

GC11P085955.

HGNC

HGNC:3188. EED.

HPA

CAB012211.

MIM

605984. gene.

neXtProt

NX_O75530.

PharmGKB

PA27624.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2319.

HOVERGEN

HBG052708.

KO

K11462.

OMA

CTTLTHP.

OrthoDB

EOG4001J7.

Gene expression databases

ArrayExpress

O75530.

Bgee

O75530.

CleanEx

HS_EED.

Genevestigator

O75530.

Family and domain databases

Gene3D

2.130.10.10. 1 hit.

InterPro

IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]

Pfam

PF00400. WD40. 2 hits.
[Graphical view]

SMART

SM00320. WD40. 6 hits.
[Graphical view]

SUPFAM

SSF50978. WD40_like. 1 hit.

PROSITE

PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 2 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

EED. human.

EvolutionaryTrace

O75530.

GenomeRNAi

8726.

NextBio

32733.

SOURCE

Search...

Entry information

Entry name

EED_HUMAN

Accession

Primary (citable) accession number: O75530
Secondary accession number(s): A8K7V5 , O00149, Q6NTH2, Q7LDA5, Q7LDG8, Q86VV2, Q9UNY7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 22, 2008
Last sequence update:	July 22, 2008
Last modified:	May 1, 2013
This is version 102 of the entry and version 2 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.