Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Polycomb protein EED

Gene

Eed

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (By similarity). Genes repressed by the PRC2/EED-EZH2 complex include HOXA7, HOXB6 and HOXC8. Plays a role in X chromosome inactivation (XCI), in which one of the two X chromosomes in female mammals is transcriptionally silenced to equalize X-linked gene dosage with XY males. Required for stable maintenance of XCI in both embryonic and extraembryonic tissues. May prevent transcriptional activation of facultative heterochromatin during differentiation. Required for development of secondary trophoblast giant cells during placental development. May regulate hippocampal synaptic plasticity in the developing brain.By similarity14 Publications

GO - Molecular functioni

  • chromatin binding Source: MGI
  • histone methyltransferase activity Source: MGI
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI

GO - Biological processi

  • histone methylation Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of histone H3-K27 methylation Source: MGI
  • regulation of adaxial/abaxial pattern formation Source: MGI
  • regulation of gene expression by genetic imprinting Source: MGI
  • spinal cord development Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-212300. PRC2 methylates histones and DNA.
R-MMU-2559580. Oxidative Stress Induced Senescence.
R-MMU-3214841. PKMTs methylate histone lysines.
R-MMU-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Polycomb protein EED
Gene namesi
Name:Eed
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:95286. Eed.

Subcellular locationi

  • Nucleus
  • Chromosome

  • Note: Localizes to the inactive X chromosome in cells of the early embryo and in stem cells of the extraembryonic trophectoderm lineage. Recruitment to the inactive X-chromosome requires XIST.

GO - Cellular componenti

  • ESC/E(Z) complex Source: UniProtKB
  • nucleolus Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
  • pronucleus Source: MGI
  • sex chromatin Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi193I → N: Hypomorphic allele. Abrogates interaction with EZH2 and impairs transcriptional repression. 2 Publications1
Mutagenesisi196L → P: Null allele. Abrogates interaction with EZH2 and impairs transcriptional repression. 3 Publications1
Mutagenesisi246L → E: Abrogates interaction with EZH2. 1 Publication1
Mutagenesisi315L → E: Impairs interaction with EZH2. 1 Publication1
Mutagenesisi316G → A: Impairs interaction with EZH2. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00003437262 – 441Polycomb protein EEDAdd BLAST440

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei2PhosphoserineBy similarity1
Modified residuei34PhosphoserineCombined sources1
Modified residuei55PhosphothreonineBy similarity1
Modified residuei66N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei66N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei66N6-methyllysine; alternateBy similarity1
Modified residuei197N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei197N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei197N6-methyllysine; alternateBy similarity1
Modified residuei268N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei268N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei268N6-methyllysine; alternateBy similarity1
Modified residuei284N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei284N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei284N6-methyllysine; alternateBy similarity1

Post-translational modificationi

Methylated. Binding to histone H1 'Lys-26' promotes mono-, di-, and trimethylation of internal lysines (By similarity).By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiQ921E6.
PaxDbiQ921E6.
PeptideAtlasiQ921E6.
PRIDEiQ921E6.

PTM databases

iPTMnetiQ921E6.
PhosphoSitePlusiQ921E6.

Expressioni

Tissue specificityi

Expressed in brain, heart, kidney, liver, lung, muscle, ovary, spleen and testis. Expressed throughout the brain.3 Publications

Developmental stagei

Maternally expressed. Expressed from E5.5, and expression remains high throughout development. Expression decreases during differentiation of embryonic stem cells (ES cells). Expression increases in prostate during prostate tumor development.3 Publications

Inductioni

Induced in embryonic stem cells (ES cells) by STAT3 and POU5F1.1 Publication

Gene expression databases

BgeeiENSMUSG00000030619.
ExpressionAtlasiQ921E6. baseline and differential.
GenevisibleiQ921E6. MM.

Interactioni

Subunit structurei

Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2 (By similarity). The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12 (By similarity). 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 (By similarity). Interacts with HDAC, HDAC2, histone H1 and YY1 (By similarity). May interact with ITGA4, ITGAE and ITGB7 (By similarity). Interacts with CDYL (By similarity). Interacts with EZH2. Interacts with KMT2A/MLL1 in adult brain. Interacts with ARNTL/BMAL1.By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ezh2Q611889EBI-904301,EBI-904311
Jarid2Q6231510EBI-904301,EBI-493592
Mtf2Q023953EBI-904301,EBI-2531578

Protein-protein interaction databases

BioGridi199384. 1175 interactors.
DIPiDIP-29523N.
IntActiQ921E6. 44 interactors.
MINTiMINT-1539279.
STRINGi10090.ENSMUSP00000102853.

Structurei

Secondary structure

1441
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi83 – 89Combined sources7
Beta strandi98 – 101Combined sources4
Beta strandi112 – 117Combined sources6
Beta strandi120 – 126Combined sources7
Beta strandi132 – 139Combined sources8
Beta strandi147 – 154Combined sources8
Turni156 – 158Combined sources3
Beta strandi161 – 167Combined sources7
Beta strandi172 – 176Combined sources5
Turni177 – 180Combined sources4
Beta strandi181 – 186Combined sources6
Beta strandi193 – 198Combined sources6
Beta strandi205 – 210Combined sources6
Beta strandi215 – 219Combined sources5
Turni220 – 223Combined sources4
Beta strandi224 – 229Combined sources6
Beta strandi239 – 244Combined sources6
Beta strandi248 – 255Combined sources8
Beta strandi260 – 267Combined sources8
Helixi268 – 279Combined sources12
Beta strandi292 – 294Combined sources3
Beta strandi298 – 301Combined sources4
Beta strandi311 – 315Combined sources5
Beta strandi318 – 322Combined sources5
Beta strandi324 – 335Combined sources12
Turni340 – 342Combined sources3
Beta strandi350 – 357Combined sources8
Beta strandi368 – 370Combined sources3
Beta strandi376 – 380Combined sources5
Beta strandi386 – 390Combined sources5
Beta strandi393 – 395Combined sources3
Helixi396 – 398Combined sources3
Beta strandi401 – 404Combined sources4
Beta strandi413 – 418Combined sources6
Beta strandi422 – 429Combined sources8
Beta strandi432 – 438Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QXVX-ray1.82A81-441[»]
ProteinModelPortaliQ921E6.
SMRiQ921E6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ921E6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati91 – 134WD 1Add BLAST44
Repeati142 – 185WD 2Add BLAST44
Repeati188 – 228WD 3Add BLAST41
Repeati234 – 275WD 4Add BLAST42
Repeati304 – 341WD 5Add BLAST38
Repeati359 – 399WD 6Add BLAST41
Repeati408 – 441WD 7Add BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni81 – 441Interaction with EZH2Add BLAST361

Domaini

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 (By similarity).By similarity

Sequence similaritiesi

Belongs to the WD repeat ESC family.Curated
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG1034. Eukaryota.
ENOG410XRQI. LUCA.
GeneTreeiENSGT00510000047334.
HOGENOMiHOG000005759.
HOVERGENiHBG052708.
InParanoidiQ921E6.
KOiK11462.
OMAiCTTLTHP.
OrthoDBiEOG091G082Z.
PhylomeDBiQ921E6.
TreeFamiTF314451.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00400. WD40. 2 hits.
[Graphical view]
SMARTiSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 2 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative initiation. AlignAdd to basket

Note: Additional isoforms may be produced by alternative initiation from other non-canonical start codons but their precise positions have not been unambiguously determined.2 Publications
Isoform 1 (identifier: Q921E6-1) [UniParc]FASTAAdd to basket
Also known as: EED-3

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.

« Hide

        10         20         30         40         50
MSEREVSTAP AGTDMPAAKK QKLSSDENSN PDLSGDENDD AVSIESGTNT
60 70 80 90 100
ERPDTPTNTP NAPGRKSWGK GKWKSKKCKY SFKCVNSLKE DHNQPLFGVQ
110 120 130 140 150
FNWHSKEGDP LVFATVGSNR VTLYECHSQG EIRLLQSYVD ADADENFYTC
160 170 180 190 200
AWTYDSNTSH PLLAVAGSRG IIRIINPITM QCIKHYVGHG NAINELKFHP
210 220 230 240 250
RDPNLLLSVS KDHALRLWNI QTDTLVAIFG GVEGHRDEVL SADYDLLGEK
260 270 280 290 300
IMSCGMDHSL KLWRINSKRM MNAIKESYDY NPNKTNRPFI SQKIHFPDFS
310 320 330 340 350
TRDIHRNYVD CVRWLGDLIL SKSCENAIVC WKPGKMEDDI DKIKPSESNV
360 370 380 390 400
TILGRFDYSQ CDIWYMRFSM DFWQKMLALG NQVGKLYVWD LEVEDPHKAK
410 420 430 440
CTTLTHHKCG AAIRQTSFSR DSSILIAVCD DASIWRWDRL R
Length:441
Mass (Da):50,198
Last modified:December 1, 2001 - v1
Checksum:iD2E0A5BA27C0499A
GO
Isoform 2 (identifier: Q921E6-2) [UniParc]FASTAAdd to basket
Also known as: EED-1

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAGSHARPPRRLGAICDSGGSGGGGGAGSFAAGSGRACLTAVWRRPRPRRQEPGGRRRNM

Note: Translation initiates from a non-canonical start codon (GUG).
Show »
Length:500
Mass (Da):56,194
Checksum:iEC7081363459B105
GO
Isoform 3 (identifier: Q921E6-3) [UniParc]FASTAAdd to basket
Also known as: EED-4

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.

Show »
Length:427
Mass (Da):48,765
Checksum:i794AABBF7BB46B99
GO

Sequence cautioni

The sequence AAB38319 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAC53302 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH12966 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0346931 – 14Missing in isoform 3. CuratedAdd BLAST14
Alternative sequenceiVSP_0346941M → MAGSHARPPRRLGAICDSGG SGGGGGAGSFAAGSGRACLT AVWRRPRPRRQEPGGRRRNM in isoform 2. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78103 mRNA. Translation: AAB38319.1. Different initiation.
U97675 mRNA. Translation: AAC53302.1. Different initiation.
AK077664 mRNA. Translation: BAC36938.1.
AK131976 mRNA. Translation: BAE20916.1.
AK133890 mRNA. Translation: BAE21915.1.
BC012966 mRNA. Translation: AAH12966.1. Different initiation.
CCDSiCCDS40016.1. [Q921E6-1]
RefSeqiNP_068676.1. NM_021876.3. [Q921E6-1]
UniGeneiMm.380914.

Genome annotation databases

EnsembliENSMUST00000107234; ENSMUSP00000102853; ENSMUSG00000030619. [Q921E6-1]
GeneIDi13626.
KEGGimmu:13626.
UCSCiuc009igk.2. mouse. [Q921E6-1]

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78103 mRNA. Translation: AAB38319.1. Different initiation.
U97675 mRNA. Translation: AAC53302.1. Different initiation.
AK077664 mRNA. Translation: BAC36938.1.
AK131976 mRNA. Translation: BAE20916.1.
AK133890 mRNA. Translation: BAE21915.1.
BC012966 mRNA. Translation: AAH12966.1. Different initiation.
CCDSiCCDS40016.1. [Q921E6-1]
RefSeqiNP_068676.1. NM_021876.3. [Q921E6-1]
UniGeneiMm.380914.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QXVX-ray1.82A81-441[»]
ProteinModelPortaliQ921E6.
SMRiQ921E6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199384. 1175 interactors.
DIPiDIP-29523N.
IntActiQ921E6. 44 interactors.
MINTiMINT-1539279.
STRINGi10090.ENSMUSP00000102853.

PTM databases

iPTMnetiQ921E6.
PhosphoSitePlusiQ921E6.

Proteomic databases

EPDiQ921E6.
PaxDbiQ921E6.
PeptideAtlasiQ921E6.
PRIDEiQ921E6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000107234; ENSMUSP00000102853; ENSMUSG00000030619. [Q921E6-1]
GeneIDi13626.
KEGGimmu:13626.
UCSCiuc009igk.2. mouse. [Q921E6-1]

Organism-specific databases

CTDi8726.
MGIiMGI:95286. Eed.

Phylogenomic databases

eggNOGiKOG1034. Eukaryota.
ENOG410XRQI. LUCA.
GeneTreeiENSGT00510000047334.
HOGENOMiHOG000005759.
HOVERGENiHBG052708.
InParanoidiQ921E6.
KOiK11462.
OMAiCTTLTHP.
OrthoDBiEOG091G082Z.
PhylomeDBiQ921E6.
TreeFamiTF314451.

Enzyme and pathway databases

ReactomeiR-MMU-212300. PRC2 methylates histones and DNA.
R-MMU-2559580. Oxidative Stress Induced Senescence.
R-MMU-3214841. PKMTs methylate histone lysines.
R-MMU-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.

Miscellaneous databases

ChiTaRSiEed. mouse.
EvolutionaryTraceiQ921E6.
PROiQ921E6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030619.
ExpressionAtlasiQ921E6. baseline and differential.
GenevisibleiQ921E6. MM.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00400. WD40. 2 hits.
[Graphical view]
SMARTiSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 2 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEED_MOUSE
AccessioniPrimary (citable) accession number: Q921E6
Secondary accession number(s): P97462
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Mice homozygous for a null allele of this protein (Pro-196) exhibit disrupted anterior posterior patterning of the primitive streak during gastrulation and reduced numbers of trophoblast giant cells. Mice homozygous for a hypomorphic allele of this protein (Asn-193) exhibit posterior transformations along the axial skeleton and altered patterns of Hox gene expression.

Caution

Was originally thought (PubMed:9234727) to interact with HNRNPK. This apparent interaction may be mediated by the translated product of the 5'-UTR sequence of the 2-hybrid clone.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

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