EED_HUMAN
ID EED_HUMAN Reviewed; 441 AA.
AC O75530; A8K7V5; O00149; Q6NTH2; Q7LDA5; Q7LDG8; Q86VV2; Q9UNY7;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Polycomb protein EED {ECO:0000305};
DE Short=hEED;
DE AltName: Full=Embryonic ectoderm development protein {ECO:0000303|PubMed:28229514};
DE AltName: Full=WD protein associating with integrin cytoplasmic tails 1;
DE Short=WAIT-1;
GN Name=EED {ECO:0000312|HGNC:HGNC:3188};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9806832; DOI=10.1006/geno.1998.5509;
RA Schumacher A., Lichtarge O., Schwartz S., Magnuson T.;
RT "The murine Polycomb-group gene eed and its human orthologue: functional
RT implications of evolutionary conservation.";
RL Genomics 54:79-88(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH EZH2,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ILE-193 AND
RP LEU-196, AND PUTATIVE ALTERNATIVE INITIATION.
RX PubMed=9584199; DOI=10.1128/mcb.18.6.3586;
RA Sewalt R.G.A.B., van der Vlag J., Gunster M.J., Hamer K.M.,
RA den Blaauwen J.L., Satijn D.P.E., Hendrix T., van Driel R., Otte A.P.;
RT "Characterization of interactions between the mammalian polycomb-group
RT proteins Enx1/EZH2 and EED suggests the existence of different mammalian
RT polycomb-group protein complexes.";
RL Mol. Cell. Biol. 18:3586-3595(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), INTERACTION WITH THE HIV-1
RP MA PROTEIN, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 300-SER-THR-301 AND 305-HIS-TYR-308.
RC TISSUE=Spleen;
RX PubMed=9880543; DOI=10.1074/jbc.274.3.1635;
RA Peytavi R., Hong S.S., Gay B., d'Angeac A.D., Selig L., Benichou S.,
RA Benarous R., Boulanger P.;
RT "HEED, the product of the human homolog of the murine eed gene, binds to
RT the matrix protein of HIV-1.";
RL J. Biol. Chem. 274:1635-1645(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 15-441 (ISOFORM 1).
RC TISSUE=Eye, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-441 (ISOFORM 1), INTERACTION WITH ITGA4;
RP ITGAE AND ITGB7, AND TISSUE SPECIFICITY.
RX PubMed=9765275; DOI=10.1074/jbc.273.42.27459;
RA Rietzler M., Bittner M., Kolanus W., Schuster A., Holzmann B.;
RT "The human WD repeat protein WAIT-1 specifically interacts with the
RT cytoplasmic tails of beta7-integrins.";
RL J. Biol. Chem. 273:27459-27466(1998).
RN [9]
RP FUNCTION, AND INTERACTION WITH EZH2; HDAC1 AND HDAC2.
RX PubMed=10581039; DOI=10.1038/70602;
RA van der Vlag J., Otte A.P.;
RT "Transcriptional repression mediated by the human polycomb-group protein
RT EED involves histone deacetylation.";
RL Nat. Genet. 23:474-478(1999).
RN [10]
RP INTERACTION WITH EZH2 AND YY1.
RX PubMed=11158321; DOI=10.1128/mcb.21.4.1360-1369.2001;
RA Satijn D.P.E., Hamer K.M., den Blaauwen J., Otte A.P.;
RT "The polycomb group protein EED interacts with YY1, and both proteins
RT induce neural tissue in Xenopus embryos.";
RL Mol. Cell. Biol. 21:1360-1369(2001).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX
RP WITH EZH2; RBBP4; RBBP7 AND SUZ12, AND METHYLTRANSFERASE ACTIVITY OF THE
RP PRC2 COMPLEX.
RX PubMed=12435631; DOI=10.1101/gad.1035902;
RA Kuzmichev A., Nishioka K., Erdjument-Bromage H., Tempst P., Reinberg D.;
RT "Histone methyltransferase activity associated with a human multiprotein
RT complex containing the Enhancer of Zeste protein.";
RL Genes Dev. 16:2893-2905(2002).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=12101246; DOI=10.1128/mcb.22.15.5539-5553.2002;
RA Sewalt R.G.A.B., Lachner M., Vargas M., Hamer K.M., den Blaauwen J.L.,
RA Hendrix T., Melcher M., Schweizer D., Jenuwein T., Otte A.P.;
RT "Selective interactions between vertebrate polycomb homologs and the
RT SUV39H1 histone lysine methyltransferase suggest that histone H3-K9
RT methylation contributes to chromosomal targeting of Polycomb group
RT proteins.";
RL Mol. Cell. Biol. 22:5539-5553(2002).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX
RP WITH EZH2; RBBP4; RBBP7 AND SUZ12, AND METHYLTRANSFERASE ACTIVITY OF THE
RP PRC2 COMPLEX.
RX PubMed=12351676; DOI=10.1126/science.1076997;
RA Cao R., Wang L., Wang H., Xia L., Erdjument-Bromage H., Tempst P.,
RA Jones R.S., Zhang Y.;
RT "Role of histone H3 lysine 27 methylation in Polycomb-group silencing.";
RL Science 298:1039-1043(2002).
RN [14]
RP FUNCTION, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=14532106; DOI=10.1093/emboj/cdg542;
RA Bracken A.P., Pasini D., Capra M., Prosperini E., Colli E., Helin K.;
RT "EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and
RT amplified in cancer.";
RL EMBO J. 22:5323-5335(2003).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=12649488; DOI=10.1126/science.1084274;
RA Plath K., Fang J., Mlynarczyk-Evans S.K., Cao R., Worringer K.A., Wang H.,
RA de la Cruz C.C., Otte A.P., Panning B., Zhang Y.;
RT "Role of histone H3 lysine 27 methylation in X inactivation.";
RL Science 300:131-135(2003).
RN [16]
RP FUNCTION, INTERACTION WITH EZH2, AND METHYLTRANSFERASE ACTIVITY OF THE PRC2
RP COMPLEX.
RX PubMed=15385962; DOI=10.1038/sj.emboj.7600402;
RA Pasini D., Bracken A.P., Jensen M.R., Lazzerini Denchi E., Helin K.;
RT "Suz12 is essential for mouse development and for EZH2 histone
RT methyltransferase activity.";
RL EMBO J. 23:4061-4071(2004).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15231737; DOI=10.1101/gad.1200204;
RA Kirmizis A., Bartley S.M., Kuzmichev A., Margueron R., Reinberg D.,
RA Green R., Farnham P.J.;
RT "Silencing of human polycomb target genes is associated with methylation of
RT histone H3 Lys 27.";
RL Genes Dev. 18:1592-1605(2004).
RN [18]
RP CHARACTERIZATION OF THE PRC2 AND PRC3 COMPLEXES INCLUDING EED; EZH2; RBBP4;
RP RBBP7 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 AND PRC3 COMPLEXES,
RP AND PUTATIVE ALTERNATIVE INITIATION.
RX PubMed=15099518; DOI=10.1016/s1097-2765(04)00185-6;
RA Kuzmichev A., Jenuwein T., Tempst P., Reinberg D.;
RT "Different EZH2-containing complexes target methylation of histone H1 or
RT nucleosomal histone H3.";
RL Mol. Cell 14:183-193(2004).
RN [19]
RP FUNCTION, CHARACTERIZATION OF THE PRC2 COMPLEX INCLUDING AEBP2; EED; EZH2;
RP RBBP4 AND SUZ12, AND METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
RX PubMed=15225548; DOI=10.1016/j.molcel.2004.06.020;
RA Cao R., Zhang Y.;
RT "SUZ12 is required for both the histone methyltransferase activity and the
RT silencing function of the EED-EZH2 complex.";
RL Mol. Cell 15:57-67(2004).
RN [20]
RP CHARACTERIZATION OF THE PRC4 COMPLEX INCLUDING EED; EZH2; RBBP4; RBBP7;
RP SUZ12 AND SIRT1, METHYLTRANSFERASE ACTIVITY OF THE PRC4 COMPLEX, AND TISSUE
RP SPECIFICITY.
RX PubMed=15684044; DOI=10.1073/pnas.0409875102;
RA Kuzmichev A., Margueron R., Vaquero A., Preissner T.S., Scher M.,
RA Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P.J.,
RA Reinberg D.;
RT "Composition and histone substrates of polycomb repressive group complexes
RT change during cellular differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005).
RN [21]
RP METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX, AND INTERACTION WITH
RP HISTONE H1.
RX PubMed=16431907; DOI=10.1074/jbc.m513425200;
RA Martin C., Cao R., Zhang Y.;
RT "Substrate preferences of the EZH2 histone methyltransferase complex.";
RL J. Biol. Chem. 281:8365-8370(2006).
RN [22]
RP FUNCTION, AND INTERACTION OF THE PRC2 COMPLEX WITH DNMT1; DNMT3A AND
RP DNMT3B.
RX PubMed=16357870; DOI=10.1038/nature04431;
RA Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C.,
RA Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M.,
RA Esteller M., Di Croce L., de Launoit Y., Fuks F.;
RT "The Polycomb group protein EZH2 directly controls DNA methylation.";
RL Nature 439:871-874(2006).
RN [23]
RP ERRATUM OF PUBMED:16357870.
RA Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C.,
RA Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M.,
RA Esteller M., Di Croce L., de Launoit Y., Fuks F.;
RL Nature 446:824-824(2007).
RN [24]
RP DE NOVO DNA METHYLATION OF PRC2 TARGET GENES.
RX PubMed=17200670; DOI=10.1038/ng1950;
RA Schlesinger Y., Straussman R., Keshet I., Farkash S., Hecht M.,
RA Zimmerman J., Eden E., Yakhini Z., Ben-Shushan E., Reubinoff B.E.,
RA Bergman Y., Simon I., Cedar H.;
RT "Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for
RT de novo methylation in cancer.";
RL Nat. Genet. 39:232-236(2007).
RN [25]
RP IDENTIFICATION IN THE PRC2/EED-EZH1 COMPLEX.
RX PubMed=19026781; DOI=10.1016/j.molcel.2008.11.004;
RA Margueron R., Li G., Sarma K., Blais A., Zavadil J., Woodcock C.L.,
RA Dynlacht B.D., Reinberg D.;
RT "Ezh1 and Ezh2 maintain repressive chromatin through different
RT mechanisms.";
RL Mol. Cell 32:503-518(2008).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION OF THE PRC2 COMPLEX WITH
RP PHF1, AND METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
RX PubMed=18086877; DOI=10.1128/mcb.01589-07;
RA Cao R., Wang H., He J., Erdjument-Bromage H., Tempst P., Zhang Y.;
RT "Role of hPHF1 in H3K27 methylation and Hox gene silencing.";
RL Mol. Cell. Biol. 28:1862-1872(2008).
RN [27]
RP FUNCTION, INTERACTION WITH EZH2 AND SUZ12, INTERACTION OF THE PRC2 COMPLEX
RP WITH PHF1, AND METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
RX PubMed=18285464; DOI=10.1128/mcb.02017-07;
RA Sarma K., Margueron R., Ivanov A., Pirrotta V., Reinberg D.;
RT "Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in
RT vivo.";
RL Mol. Cell. Biol. 28:2718-2731(2008).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-55, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [30]
RP INTERACTION WITH CDYL.
RX PubMed=22009739; DOI=10.1074/jbc.m111.271064;
RA Zhang Y., Yang X., Gui B., Xie G., Zhang D., Shang Y., Liang J.;
RT "Corepressor protein CDYL functions as a molecular bridge between polycomb
RT repressor complex 2 and repressive chromatin mark trimethylated histone
RT lysine 27.";
RL J. Biol. Chem. 286:42414-42425(2011).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [33]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 40-441 ALONE AND IN COMPLEX WITH
RP METHYLATED HISTONE PEPTIDES, FUNCTION, DOMAIN WD REPEATS, METHYLATION AT
RP LYS-66; LYS-197; LYS-268 AND LYS-284, AND MUTAGENESIS OF PHE-97; TYR-148;
RP TRP-364 AND TYR-365.
RX PubMed=20974918; DOI=10.1073/pnas.1008937107;
RA Xu C., Bian C., Yang W., Galka M., Ouyang H., Chen C., Qiu W., Liu H.,
RA Jones A.E., MacKenzie F., Pan P., Li S.S., Wang H., Min J.;
RT "Binding of different histone marks differentially regulates the activity
RT and specificity of polycomb repressive complex 2 (PRC2).";
RL Proc. Natl. Acad. Sci. U.S.A. 107:19266-19271(2010).
RN [35]
RP INVOLVEMENT IN COGIS, AND VARIANT COGIS SER-302.
RX PubMed=25787343; DOI=10.1038/jhg.2015.26;
RA Cohen A.S., Tuysuz B., Shen Y., Bhalla S.K., Jones S.J., Gibson W.T.;
RT "A novel mutation in EED associated with overgrowth.";
RL J. Hum. Genet. 60:339-342(2015).
RN [36]
RP VARIANT COGIS TYR-258.
RX PubMed=27193220; DOI=10.1038/jhg.2016.51;
RA Cohen A.S., Gibson W.T.;
RT "EED-associated overgrowth in a second male patient.";
RL J. Hum. Genet. 61:831-834(2016).
RN [37]
RP VARIANTS COGIS SER-194 AND GLY-236.
RX PubMed=28475857; DOI=10.1016/j.ajhg.2017.03.010;
RG Childhood Overgrowth Collaboration;
RA Tatton-Brown K., Loveday C., Yost S., Clarke M., Ramsay E., Zachariou A.,
RA Elliott A., Wylie H., Ardissone A., Rittinger O., Stewart F., Temple I.K.,
RA Cole T., Mahamdallie S., Seal S., Ruark E., Rahman N.;
RT "Mutations in epigenetic regulation genes are a major cause of overgrowth
RT with intellectual disability.";
RL Am. J. Hum. Genet. 100:725-736(2017).
RN [38]
RP VARIANT COGIS GLY-302.
RX PubMed=27868325; DOI=10.1002/ajmg.a.38055;
RA Cooney E., Bi W., Schlesinger A.E., Vinson S., Potocki L.;
RT "Novel EED mutation in patient with Weaver syndrome.";
RL Am. J. Med. Genet. A 173:541-545(2017).
RN [39]
RP VARIANT COGIS THR-236, CHARACTERIZATION OF VARIANTS COGIS THR-236 AND
RP SER-302, AND FUNCTION.
RX PubMed=28229514; DOI=10.1002/humu.23200;
RA Imagawa E., Higashimoto K., Sakai Y., Numakura C., Okamoto N.,
RA Matsunaga S., Ryo A., Sato Y., Sanefuji M., Ihara K., Takada Y.,
RA Nishimura G., Saitsu H., Mizuguchi T., Miyatake S., Nakashima M.,
RA Miyake N., Soejima H., Matsumoto N.;
RT "Mutations in genes encoding polycomb repressive complex 2 subunits cause
RT Weaver syndrome.";
RL Hum. Mutat. 38:637-648(2017).
CC -!- FUNCTION: Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2
CC complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading
CC to transcriptional repression of the affected target gene. Also
CC recognizes 'Lys-26' trimethylated histone H1 with the effect of
CC inhibiting PRC2 complex methyltransferase activity on nucleosomal
CC histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite
CC effect, enabling the propagation of this repressive mark. The PRC2/EED-
CC EZH2 complex may also serve as a recruiting platform for DNA
CC methyltransferases, thereby linking two epigenetic repression systems.
CC Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1
CC and CDKN2A. {ECO:0000269|PubMed:10581039, ECO:0000269|PubMed:14532106,
CC ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737,
CC ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16357870,
CC ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:20974918,
CC ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:9584199}.
CC -!- SUBUNIT: Component of the PRC2/EED-EZH2 complex, which includes EED,
CC EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The minimum components
CC required for methyltransferase activity of the PRC2/EED-EZH2 complex
CC are EED, EZH2 and SUZ12. Component of the PRC2/EED-EZH1 complex, which
CC includes EED, EZH1, SUZ12, RBBP4 and AEBP2. The PRC2 complex may also
CC interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and
CC with SIRT1 via the SUZ12 subunit. Interacts with HDAC, HDAC2, histone
CC H1 and YY1. May interact with ITGA4, ITGAE and ITGB7. Interacts with
CC CDYL. Interacts with ARNTL/BMAL1. Interacts with KMT2A/MLL1 (By
CC similarity). {ECO:0000250|UniProtKB:Q921E6,
CC ECO:0000269|PubMed:10581039, ECO:0000269|PubMed:11158321,
CC ECO:0000269|PubMed:12351676, ECO:0000269|PubMed:12435631,
CC ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16357870,
CC ECO:0000269|PubMed:16431907, ECO:0000269|PubMed:18086877,
CC ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:19026781,
CC ECO:0000269|PubMed:20974918, ECO:0000269|PubMed:22009739,
CC ECO:0000269|PubMed:9584199, ECO:0000269|PubMed:9765275}.
CC -!- SUBUNIT: (Microbial infection) May interact with the MA protein of HIV-
CC 1. {ECO:0000269|PubMed:9880543}.
CC -!- INTERACTION:
CC O75530; Q8IXJ9: ASXL1; NbExp=5; IntAct=EBI-923794, EBI-1646500;
CC O75530; P49368: CCT3; NbExp=2; IntAct=EBI-923794, EBI-356673;
CC O75530; Q16531: DDB1; NbExp=4; IntAct=EBI-923794, EBI-350322;
CC O75530; P26358: DNMT1; NbExp=3; IntAct=EBI-923794, EBI-719459;
CC O75530; Q9Y6K1: DNMT3A; NbExp=2; IntAct=EBI-923794, EBI-923653;
CC O75530; Q9UBC3: DNMT3B; NbExp=4; IntAct=EBI-923794, EBI-80125;
CC O75530; O75530: EED; NbExp=2; IntAct=EBI-923794, EBI-923794;
CC O75530; Q92800: EZH1; NbExp=4; IntAct=EBI-923794, EBI-8830732;
CC O75530; Q15910: EZH2; NbExp=12; IntAct=EBI-923794, EBI-530054;
CC O75530; Q92833-1: JARID2; NbExp=4; IntAct=EBI-923794, EBI-15825247;
CC O75530; Q15156: PML-RAR; NbExp=2; IntAct=EBI-923794, EBI-867256;
CC O75530; P63244: RACK1; NbExp=3; IntAct=EBI-923794, EBI-296739;
CC O75530; Q9NY59: SMPD3; NbExp=2; IntAct=EBI-923794, EBI-715400;
CC O75530; Q15022: SUZ12; NbExp=10; IntAct=EBI-923794, EBI-1264675;
CC O75530; Q9JJY3: Smpd3; Xeno; NbExp=5; IntAct=EBI-923794, EBI-9817007;
CC O75530-2; G5E9A7: DMWD; NbExp=3; IntAct=EBI-11132357, EBI-10976677;
CC O75530-2; Q92800-2: EZH1; NbExp=3; IntAct=EBI-11132357, EBI-12322467;
CC O75530-2; Q15910-2: EZH2; NbExp=3; IntAct=EBI-11132357, EBI-10699473;
CC O75530-2; P28799: GRN; NbExp=3; IntAct=EBI-11132357, EBI-747754;
CC O75530-2; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-11132357, EBI-1055254;
CC O75530-2; O60333-2: KIF1B; NbExp=3; IntAct=EBI-11132357, EBI-10975473;
CC O75530-2; P35240: NF2; NbExp=3; IntAct=EBI-11132357, EBI-1014472;
CC O75530-2; O60260-5: PRKN; NbExp=3; IntAct=EBI-11132357, EBI-21251460;
CC O75530-2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-11132357, EBI-396669;
CC O75530-2; P37840: SNCA; NbExp=3; IntAct=EBI-11132357, EBI-985879;
CC O75530-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-11132357, EBI-5235340;
CC O75530-2; Q13148: TARDBP; NbExp=3; IntAct=EBI-11132357, EBI-372899;
CC O75530-2; P40337-2: VHL; NbExp=3; IntAct=EBI-11132357, EBI-12157263;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Transiently colocalizes
CC with XIST at inactive X chromosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Comment=Additional isoforms may be produced by alternative
CC initiation, both from non-canonical start codons upstream of the
CC initiator methionine displayed and from other canonical start codons
CC downstream of that displayed (PubMed:15099518 and PubMed:15684044).
CC The precise sites of translation initiation have not been
CC unambiguously identified.;
CC Name=1;
CC IsoId=O75530-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75530-2; Sequence=VSP_034691;
CC Name=3;
CC IsoId=O75530-3; Sequence=VSP_034692;
CC -!- TISSUE SPECIFICITY: Expressed in brain, colon, heart, kidney, liver,
CC lung, muscle, ovary, peripheral blood leukocytes, pancreas, placenta,
CC prostate, spleen, small intestine, testis, thymus and uterus. Appears
CC to be overexpressed in breast and colon cancer.
CC {ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:9584199,
CC ECO:0000269|PubMed:9765275, ECO:0000269|PubMed:9806832,
CC ECO:0000269|PubMed:9880543}.
CC -!- DEVELOPMENTAL STAGE: Expression peaks at the G1/S phase boundary.
CC {ECO:0000269|PubMed:14532106}.
CC -!- INDUCTION: Expression is induced by E2F1, E2F2 and E2F3.
CC {ECO:0000269|PubMed:14532106}.
CC -!- DOMAIN: The WD repeat domain mediates recognition of trimethylated
CC histone peptides at the consensus sequence Ala-Arg-Lys-Ser. This is
CC achieved through an aromatic cage encircling the methyllysine, and
CC involving Phe-97, Tyr-148 and Tyr-365. {ECO:0000269|PubMed:20974918}.
CC -!- PTM: Methylated. Binding to histone H1 'Lys-26' promotes mono-, di-,
CC and trimethylation of internal lysines. {ECO:0000269|PubMed:20974918}.
CC -!- DISEASE: Cohen-Gibson syndrome (COGIS) [MIM:617561]: An autosomal
CC dominant overgrowth disorder characterized by accelerated osseous
CC maturation, advanced bone age, skeletal abnormalities including flaring
CC of the metaphyses of the long bones, large hands with long fingers and
CC camptodactyly, scoliosis, cervical spine anomalies, dysmorphic facial
CC features, and variable intellectual disability.
CC {ECO:0000269|PubMed:25787343, ECO:0000269|PubMed:27193220,
CC ECO:0000269|PubMed:27868325, ECO:0000269|PubMed:28229514,
CC ECO:0000269|PubMed:28475857}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the WD repeat ESC family. {ECO:0000305}.
CC -!- CAUTION: Two variants of the PRC2 complex have been described, termed
CC PRC3 and PRC4. Each of the three complexes may include a different
CC complement of EED isoforms, although the precise sequences of the
CC isoforms in each complex have not been determined. The PRC2 and PRC4
CC complexes may also methylate 'Lys-26' of histone H1 in addition to
CC 'Lys-27' of histone H3 (PubMed:15099518 and PubMed:15684044), although
CC other studies have demonstrated no methylation of 'Lys-26' of histone
CC H1 by PRC2 (PubMed:16431907). {ECO:0000305|PubMed:16431907}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC23685.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC68675.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AF080227; AAC95144.1; -; mRNA.
DR EMBL; AF070418; AAC23685.1; ALT_INIT; mRNA.
DR EMBL; U90651; AAD08714.1; -; mRNA.
DR EMBL; AF099032; AAD08815.1; -; mRNA.
DR EMBL; AK292120; BAF84809.1; -; mRNA.
DR EMBL; AP003084; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW75129.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW75130.1; -; Genomic_DNA.
DR EMBL; BC047672; AAH47672.1; -; mRNA.
DR EMBL; BC068995; AAH68995.1; -; mRNA.
DR EMBL; AF078933; AAC68675.1; ALT_INIT; mRNA.
DR CCDS; CCDS76463.1; -. [O75530-2]
DR CCDS; CCDS8273.1; -. [O75530-1]
DR RefSeq; NP_001294936.1; NM_001308007.1. [O75530-2]
DR RefSeq; NP_003788.2; NM_003797.4. [O75530-1]
DR PDB; 3IIW; X-ray; 1.80 A; A=77-441.
DR PDB; 3IIY; X-ray; 2.65 A; A=77-441.
DR PDB; 3IJ0; X-ray; 2.45 A; A=77-441.
DR PDB; 3IJ1; X-ray; 2.10 A; A=77-441.
DR PDB; 3IJC; X-ray; 1.95 A; A=77-441.
DR PDB; 3JPX; X-ray; 2.05 A; A=40-441.
DR PDB; 3JZG; X-ray; 2.10 A; A=40-441.
DR PDB; 3JZH; X-ray; 2.05 A; A=40-441.
DR PDB; 3JZN; X-ray; 2.60 A; A=76-441.
DR PDB; 3K26; X-ray; 1.58 A; A=76-441.
DR PDB; 3K27; X-ray; 1.76 A; A=76-441.
DR PDB; 4W2R; X-ray; 2.81 A; E/F=81-441.
DR PDB; 4X3E; X-ray; 2.30 A; A=77-441.
DR PDB; 5GSA; X-ray; 2.49 A; A/B=76-441.
DR PDB; 5H13; X-ray; 1.90 A; A=76-441.
DR PDB; 5H14; X-ray; 1.90 A; A/B=76-441.
DR PDB; 5H15; X-ray; 2.27 A; A/B=76-441.
DR PDB; 5H17; X-ray; 2.30 A; A=76-441.
DR PDB; 5H19; X-ray; 1.90 A; A=76-441.
DR PDB; 5H24; X-ray; 2.50 A; A/B=76-441.
DR PDB; 5H25; X-ray; 2.88 A; A/B=76-441.
DR PDB; 5HYN; X-ray; 2.95 A; B/G/L/R=77-441.
DR PDB; 5IJ7; X-ray; 2.62 A; E/F=81-441.
DR PDB; 5IJ8; X-ray; 2.99 A; E/F=81-441.
DR PDB; 5K0M; X-ray; 1.83 A; A=77-441.
DR PDB; 5LS6; X-ray; 3.47 A; B/E/H/K=77-441.
DR PDB; 5TTW; X-ray; 1.74 A; A/C=76-441.
DR PDB; 5U5H; X-ray; 1.80 A; A=76-441.
DR PDB; 5U5K; X-ray; 2.33 A; A=76-441.
DR PDB; 5U5T; X-ray; 1.60 A; A/B=76-441.
DR PDB; 5U62; X-ray; 1.90 A; A/B=76-441.
DR PDB; 5U69; X-ray; 1.28 A; A=77-441.
DR PDB; 5U6D; X-ray; 1.64 A; A=77-441.
DR PDB; 5U8A; X-ray; 1.45 A; A=77-441.
DR PDB; 5U8F; X-ray; 1.34 A; A=77-441.
DR PDB; 5WG6; X-ray; 3.90 A; B/D=2-441.
DR PDB; 5WP3; X-ray; 2.55 A; A=75-441.
DR PDB; 5WUK; X-ray; 2.03 A; A=76-441.
DR PDB; 6B3W; X-ray; 3.05 A; E/F=81-441.
DR PDB; 6C23; EM; 3.90 A; L=1-441.
DR PDB; 6C24; EM; 3.50 A; L=1-441.
DR PDB; 6LO2; X-ray; 2.21 A; A/B=76-441.
DR PDB; 6SFB; X-ray; 1.52 A; A/B=76-441.
DR PDB; 6SFC; X-ray; 2.00 A; A/B=76-441.
DR PDB; 6U4Y; X-ray; 2.91 A; D/E/F=78-441.
DR PDB; 6V3X; X-ray; 1.70 A; A=75-441.
DR PDB; 6V3Y; X-ray; 1.63 A; A=81-439.
DR PDB; 6W7F; X-ray; 2.20 A; A=77-441.
DR PDB; 6W7G; X-ray; 1.85 A; A=77-441.
DR PDB; 6WKR; EM; 3.50 A; L=1-441.
DR PDB; 6YVI; X-ray; 2.26 A; A/B=76-441.
DR PDB; 6YVJ; X-ray; 1.84 A; A/B=76-441.
DR PDB; 7KSO; EM; 3.90 A; B=1-441.
DR PDB; 7KSR; EM; 4.10 A; B=1-441.
DR PDB; 7KTP; EM; 4.80 A; B=1-441.
DR PDB; 7KXT; X-ray; 2.15 A; A/B=40-441.
DR PDB; 7MSB; X-ray; 1.90 A; A=77-441.
DR PDB; 7MSD; X-ray; 2.20 A; A=77-441.
DR PDB; 7P3C; X-ray; 1.61 A; A/B=76-441.
DR PDB; 7P3G; X-ray; 2.39 A; A/B=76-441.
DR PDB; 7P3J; X-ray; 1.93 A; A/B=76-441.
DR PDB; 7QJG; X-ray; 1.80 A; A/B=77-441.
DR PDB; 7QJU; X-ray; 1.80 A; A/B=77-441.
DR PDB; 7QK4; X-ray; 1.60 A; A=77-441.
DR PDBsum; 3IIW; -.
DR PDBsum; 3IIY; -.
DR PDBsum; 3IJ0; -.
DR PDBsum; 3IJ1; -.
DR PDBsum; 3IJC; -.
DR PDBsum; 3JPX; -.
DR PDBsum; 3JZG; -.
DR PDBsum; 3JZH; -.
DR PDBsum; 3JZN; -.
DR PDBsum; 3K26; -.
DR PDBsum; 3K27; -.
DR PDBsum; 4W2R; -.
DR PDBsum; 4X3E; -.
DR PDBsum; 5GSA; -.
DR PDBsum; 5H13; -.
DR PDBsum; 5H14; -.
DR PDBsum; 5H15; -.
DR PDBsum; 5H17; -.
DR PDBsum; 5H19; -.
DR PDBsum; 5H24; -.
DR PDBsum; 5H25; -.
DR PDBsum; 5HYN; -.
DR PDBsum; 5IJ7; -.
DR PDBsum; 5IJ8; -.
DR PDBsum; 5K0M; -.
DR PDBsum; 5LS6; -.
DR PDBsum; 5TTW; -.
DR PDBsum; 5U5H; -.
DR PDBsum; 5U5K; -.
DR PDBsum; 5U5T; -.
DR PDBsum; 5U62; -.
DR PDBsum; 5U69; -.
DR PDBsum; 5U6D; -.
DR PDBsum; 5U8A; -.
DR PDBsum; 5U8F; -.
DR PDBsum; 5WG6; -.
DR PDBsum; 5WP3; -.
DR PDBsum; 5WUK; -.
DR PDBsum; 6B3W; -.
DR PDBsum; 6C23; -.
DR PDBsum; 6C24; -.
DR PDBsum; 6LO2; -.
DR PDBsum; 6SFB; -.
DR PDBsum; 6SFC; -.
DR PDBsum; 6U4Y; -.
DR PDBsum; 6V3X; -.
DR PDBsum; 6V3Y; -.
DR PDBsum; 6W7F; -.
DR PDBsum; 6W7G; -.
DR PDBsum; 6WKR; -.
DR PDBsum; 6YVI; -.
DR PDBsum; 6YVJ; -.
DR PDBsum; 7KSO; -.
DR PDBsum; 7KSR; -.
DR PDBsum; 7KTP; -.
DR PDBsum; 7KXT; -.
DR PDBsum; 7MSB; -.
DR PDBsum; 7MSD; -.
DR PDBsum; 7P3C; -.
DR PDBsum; 7P3G; -.
DR PDBsum; 7P3J; -.
DR PDBsum; 7QJG; -.
DR PDBsum; 7QJU; -.
DR PDBsum; 7QK4; -.
DR AlphaFoldDB; O75530; -.
DR SMR; O75530; -.
DR BioGRID; 114265; 595.
DR CORUM; O75530; -.
DR DIP; DIP-36673N; -.
DR IntAct; O75530; 88.
DR MINT; O75530; -.
DR STRING; 9606.ENSP00000263360; -.
DR BindingDB; O75530; -.
DR ChEMBL; CHEMBL2189117; -.
DR DrugCentral; O75530; -.
DR GuidetoPHARMACOLOGY; 2487; -.
DR iPTMnet; O75530; -.
DR MetOSite; O75530; -.
DR PhosphoSitePlus; O75530; -.
DR BioMuta; EED; -.
DR EPD; O75530; -.
DR jPOST; O75530; -.
DR MassIVE; O75530; -.
DR MaxQB; O75530; -.
DR PaxDb; O75530; -.
DR PeptideAtlas; O75530; -.
DR PRIDE; O75530; -.
DR ProteomicsDB; 50068; -. [O75530-1]
DR ProteomicsDB; 50069; -. [O75530-2]
DR ProteomicsDB; 50070; -. [O75530-3]
DR ABCD; O75530; 1 sequenced antibody.
DR Antibodypedia; 31435; 395 antibodies from 40 providers.
DR DNASU; 8726; -.
DR Ensembl; ENST00000263360.11; ENSP00000263360.6; ENSG00000074266.22. [O75530-1]
DR Ensembl; ENST00000327320.8; ENSP00000315587.4; ENSG00000074266.22. [O75530-3]
DR Ensembl; ENST00000351625.10; ENSP00000338186.5; ENSG00000074266.22. [O75530-2]
DR Ensembl; ENST00000672825.1; ENSP00000500834.1; ENSG00000074266.22. [O75530-1]
DR GeneID; 8726; -.
DR KEGG; hsa:8726; -.
DR MANE-Select; ENST00000263360.11; ENSP00000263360.6; NM_003797.5; NP_003788.2.
DR UCSC; uc001pbp.4; human. [O75530-1]
DR CTD; 8726; -.
DR DisGeNET; 8726; -.
DR GeneCards; EED; -.
DR GeneReviews; EED; -.
DR HGNC; HGNC:3188; EED.
DR HPA; ENSG00000074266; Low tissue specificity.
DR MalaCards; EED; -.
DR MIM; 605984; gene.
DR MIM; 617561; phenotype.
DR neXtProt; NX_O75530; -.
DR NIAGADS; ENSG00000074266; -.
DR OpenTargets; ENSG00000074266; -.
DR Orphanet; 3447; Weaver syndrome.
DR PharmGKB; PA27624; -.
DR VEuPathDB; HostDB:ENSG00000074266; -.
DR eggNOG; KOG1034; Eukaryota.
DR GeneTree; ENSGT00510000047334; -.
DR HOGENOM; CLU_032683_1_0_1; -.
DR InParanoid; O75530; -.
DR OMA; WSYDSVT; -.
DR OrthoDB; 1191277at2759; -.
DR PhylomeDB; O75530; -.
DR TreeFam; TF314451; -.
DR PathwayCommons; O75530; -.
DR Reactome; R-HSA-212300; PRC2 methylates histones and DNA.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6.
DR Reactome; R-HSA-9609690; HCMV Early Events.
DR Reactome; R-HSA-9710421; Defective pyroptosis.
DR SignaLink; O75530; -.
DR SIGNOR; O75530; -.
DR BioGRID-ORCS; 8726; 162 hits in 1098 CRISPR screens.
DR ChiTaRS; EED; human.
DR EvolutionaryTrace; O75530; -.
DR GeneWiki; EED; -.
DR GenomeRNAi; 8726; -.
DR Pharos; O75530; Tchem.
DR PRO; PR:O75530; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O75530; protein.
DR Bgee; ENSG00000074266; Expressed in oviduct epithelium and 113 other tissues.
DR ExpressionAtlas; O75530; baseline and differential.
DR Genevisible; O75530; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0035098; C:ESC/E(Z) complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0008047; F:enzyme activator activity; IMP:UniProtKB.
DR GO; GO:0042054; F:histone methyltransferase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:ARUK-UCL.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
DR Gene3D; 2.130.10.10; -; 1.
DR IDEAL; IID00530; -.
DR InterPro; IPR037352; Polycomb_EED.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR10253:SF5; PTHR10253:SF5; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation; Alternative splicing;
KW Chromatin regulator; Chromosome; Disease variant; Host-virus interaction;
KW Methylation; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..441
FT /note="Polycomb protein EED"
FT /id="PRO_0000343725"
FT REPEAT 91..134
FT /note="WD 1"
FT REPEAT 142..185
FT /note="WD 2"
FT REPEAT 188..228
FT /note="WD 3"
FT REPEAT 234..275
FT /note="WD 4"
FT REPEAT 304..341
FT /note="WD 5"
FT REPEAT 359..399
FT /note="WD 6"
FT REPEAT 408..441
FT /note="WD 7"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..441
FT /note="Interaction with EZH2"
FT /evidence="ECO:0000250"
FT REGION 149..303
FT /note="Required for interaction with the matrix protein MA
FT of HIV-1"
FT REGION 301..441
FT /note="Required for interaction with the matrix protein MA
FT of HIV-1"
FT COMPBIAS 41..64
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q921E6"
FT MOD_RES 55
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 66
FT /note="N6,N6,N6-trimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 66
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 66
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 197
FT /note="N6,N6,N6-trimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 197
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 197
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 268
FT /note="N6,N6,N6-trimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 268
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 268
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 284
FT /note="N6,N6,N6-trimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 284
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT MOD_RES 284
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20974918"
FT VAR_SEQ 322
FT /note="K -> KSGRAILHSHQQCMRDPVSPNLRQHL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_034691"
FT VAR_SEQ 401..441
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9880543"
FT /id="VSP_034692"
FT VARIANT 194
FT /note="N -> S (in COGIS)"
FT /evidence="ECO:0000269|PubMed:28475857"
FT /id="VAR_079255"
FT VARIANT 236
FT /note="R -> G (in COGIS)"
FT /evidence="ECO:0000269|PubMed:28475857"
FT /id="VAR_079256"
FT VARIANT 236
FT /note="R -> T (in COGIS; decreased trimethylation of 'Lys-
FT 27' of histone H3; no effect on interaction with EZH2;
FT dbSNP:rs1131692176)"
FT /evidence="ECO:0000269|PubMed:28229514"
FT /id="VAR_078316"
FT VARIANT 258
FT /note="H -> Y (in COGIS; dbSNP:rs1131692174)"
FT /evidence="ECO:0000269|PubMed:27193220"
FT /id="VAR_079257"
FT VARIANT 302
FT /note="R -> G (in COGIS; dbSNP:rs1131692175)"
FT /evidence="ECO:0000269|PubMed:27868325"
FT /id="VAR_079258"
FT VARIANT 302
FT /note="R -> S (in COGIS; decreased trimethylation of 'Lys-
FT 27' of histone H3; dbSNP:rs1131692173)"
FT /evidence="ECO:0000269|PubMed:25787343,
FT ECO:0000269|PubMed:28229514"
FT /id="VAR_078317"
FT MUTAGEN 97
FT /note="F->A: Abolishes binding to H3K27me3."
FT /evidence="ECO:0000269|PubMed:20974918"
FT MUTAGEN 148
FT /note="Y->A: Abolishes binding to H3K27me3."
FT /evidence="ECO:0000269|PubMed:20974918"
FT MUTAGEN 193
FT /note="I->N: Impairs interaction with EZH2."
FT /evidence="ECO:0000269|PubMed:9584199"
FT MUTAGEN 196
FT /note="L->P: Impairs interaction with EZH2."
FT /evidence="ECO:0000269|PubMed:9584199"
FT MUTAGEN 300..301
FT /note="ST->AA: Impairs interaction with the matrix protein
FT MA of HIV-1."
FT /evidence="ECO:0000269|PubMed:9880543"
FT MUTAGEN 305..308
FT /note="HRNY->AAAA: Impairs interaction with the matrix
FT protein MA of HIV-1."
FT /evidence="ECO:0000269|PubMed:9880543"
FT MUTAGEN 364
FT /note="W->A: Abolishes binding to H3K27me3."
FT /evidence="ECO:0000269|PubMed:20974918"
FT MUTAGEN 364
FT /note="W->L: Abolishes binding to H3K27me3."
FT /evidence="ECO:0000269|PubMed:20974918"
FT MUTAGEN 365
FT /note="Y->A: Abolishes binding to H3K27me3."
FT /evidence="ECO:0000269|PubMed:20974918"
FT CONFLICT 32
FT /note="D -> E (in Ref. 8; AAC68675)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="K -> S (in Ref. 3; AAD08714/AAD08815)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="E -> K (in Ref. 3; AAD08714/AAD08815)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="S -> G (in Ref. 4; BAF84809)"
FT /evidence="ECO:0000305"
FT STRAND 83..89
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 96..101
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:5H17"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:5U5K"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:5U69"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:6SFB"
FT STRAND 132..139
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 147..154
FT /evidence="ECO:0007829|PDB:5U69"
FT TURN 156..158
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 161..167
FT /evidence="ECO:0007829|PDB:5U69"
FT TURN 168..170
FT /evidence="ECO:0007829|PDB:6C24"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:5U69"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 182..190
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 193..198
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:6C24"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:6C24"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:5U69"
FT TURN 220..223
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 224..229
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:6V3X"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 248..255
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 260..265
FT /evidence="ECO:0007829|PDB:5U69"
FT HELIX 268..279
FT /evidence="ECO:0007829|PDB:5U69"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 298..301
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 318..322
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 324..335
FT /evidence="ECO:0007829|PDB:5U69"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 350..357
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:7P3J"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:4W2R"
FT STRAND 376..380
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 382..384
FT /evidence="ECO:0007829|PDB:4W2R"
FT STRAND 386..390
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:5U69"
FT HELIX 396..398
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 400..404
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 413..418
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 422..429
FT /evidence="ECO:0007829|PDB:5U69"
FT STRAND 432..438
FT /evidence="ECO:0007829|PDB:5U69"
SQ SEQUENCE 441 AA; 50198 MW; D2E0A5BA27C0499A CRC64;
MSEREVSTAP AGTDMPAAKK QKLSSDENSN PDLSGDENDD AVSIESGTNT ERPDTPTNTP
NAPGRKSWGK GKWKSKKCKY SFKCVNSLKE DHNQPLFGVQ FNWHSKEGDP LVFATVGSNR
VTLYECHSQG EIRLLQSYVD ADADENFYTC AWTYDSNTSH PLLAVAGSRG IIRIINPITM
QCIKHYVGHG NAINELKFHP RDPNLLLSVS KDHALRLWNI QTDTLVAIFG GVEGHRDEVL
SADYDLLGEK IMSCGMDHSL KLWRINSKRM MNAIKESYDY NPNKTNRPFI SQKIHFPDFS
TRDIHRNYVD CVRWLGDLIL SKSCENAIVC WKPGKMEDDI DKIKPSESNV TILGRFDYSQ
CDIWYMRFSM DFWQKMLALG NQVGKLYVWD LEVEDPHKAK CTTLTHHKCG AAIRQTSFSR
DSSILIAVCD DASIWRWDRL R
