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Protein

Polycomb protein EED

Gene

Eed

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

GO - Molecular functioni

GO - Biological processi

  • cellular response to leukemia inhibitory factor Source: MGI
  • chromatin silencing Source: GO_Central
  • histone methylation Source: MGI
  • negative regulation of transcription by RNA polymerase II 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

Keywordsi

Molecular functionChromatin regulator, Repressor
Biological processTranscription, 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-8943724 Regulation of PTEN gene transcription
R-MMU-8953750 Transcriptional Regulation by E2F6

Names & Taxonomyi

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

Organism-specific databases

MGIiMGI:95286 Eed

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 Expressed in 311 organ(s), highest expression level in primary oocyte
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199384, 1175 interactors
DIPiDIP-29523N
IntActiQ921E6, 47 interactors
MINTiQ921E6
STRINGi10090.ENSMUSP00000102853

Structurei

Secondary structure

1441
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
InterProiView protein in InterPro
IPR037352 Polycomb_EED
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PANTHERiPTHR10253 PTHR10253, 1 hit
PfamiView protein in Pfam
PF00400 WD40, 2 hits
SMARTiView protein in SMART
SM00320 WD40, 6 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 2 hits
PS50294 WD_REPEATS_REGION, 1 hit

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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A140LIG5A0A140LIG5_MOUSE
Polycomb protein EED
Eed
220Annotation score:
A0A140LIN6A0A140LIN6_MOUSE
Polycomb protein EED
Eed
118Annotation score:

Sequence cautioni

The sequence AAB38319 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAC53302 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH12966 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.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

Similar proteinsi

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, 47 interactors
MINTiQ921E6
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-8943724 Regulation of PTEN gene transcription
R-MMU-8953750 Transcriptional Regulation by E2F6

Miscellaneous databases

ChiTaRSiEed mouse
EvolutionaryTraceiQ921E6
PROiPR:Q921E6
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030619 Expressed in 311 organ(s), highest expression level in primary oocyte
ExpressionAtlasiQ921E6 baseline and differential
GenevisibleiQ921E6 MM

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR037352 Polycomb_EED
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PANTHERiPTHR10253 PTHR10253, 1 hit
PfamiView protein in Pfam
PF00400 WD40, 2 hits
SMARTiView protein in SMART
SM00320 WD40, 6 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 2 hits
PS50294 WD_REPEATS_REGION, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiEED_MOUSE
AccessioniPrimary (citable) accession number: Q921E6
Secondary accession number(s): P97462
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: December 1, 2001
Last modified: November 7, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

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