EED (protein)

EED
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3IIW, 3IIY, 3IJ0, 3IJ1, 3IJC, 3JPX, 3JZG, 3JZH, 3JZN, 3K26, 3K27, 4X3E, 5IJ7, 5IJ8, 5HYN
Identifiers
Aliases	EED, HWAIT1, embryonic ectoderm development
External IDs	MGI: 95286 HomoloGene: 2814 GeneCards: EED
Gene ontology Molecular function • histone methyltransferase activity • chromatin binding • protein binding • identical protein binding Cellular component • sex chromatin • ESC/E(Z) complex • nucleoplasm • chromosome • nucleolus • pronucleus • nucleus Biological process • regulation of gene expression by genetic imprinting • regulation of transcription, DNA-templated • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • negative regulation of gene expression, epigenetic • spinal cord development • positive regulation of histone H3-K27 methylation • histone methylation • negative regulation of transcription, DNA-templated • covalent chromatin modification Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8726	13626
Ensembl	ENSG00000074266	ENSMUSG00000030619
UniProt	O75530	Q921E6
RefSeq (mRNA)	NM_001308007 NM_003797 NM_152991	NM_021876
RefSeq (protein)	NP_001294936.1 NP_003788.2	NP_068676.1
Location (UCSC)	Chr 11: 86.24 – 86.28 Mb	Chr 7: 89.95 – 89.98 Mb
PubMed search	[1]	[2]
Wikidata

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Polycomb protein EED is a protein that in humans is encoded by the EED gene.^[3][4][5]

Function

Polycomb protein EED is a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein interacts with enhancer of zeste 2, the cytoplasmic tail of integrin β7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene.^[5]

Clinical significance

In humans, a de-novo mutation in EED has been reported in an individual displaying symptoms similar to those of Weaver syndrome.^[6]

Interactions

EED has been shown to interact with:

• EZH2,^[7][8][9]
• HDAC1,^[7]
• Histone deacetylase 2,^[7]
• ITGB7,^[3]
• PPP1R8,^[10] and
• TGS1.^[11]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B (Nov 1998). "The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins". J. Biol. Chem. 273 (42): 27459–66. doi:10.1074/jbc.273.42.27459. PMID 9765275.
4. Schumacher A, Lichtarge O, Schwartz S, Magnuson T (Jan 1999). "The murine Polycomb-group gene eed and its human orthologue: functional implications of evolutionary conservation". Genomics. 54 (1): 79–88. doi:10.1006/geno.1998.5509. PMID 9806832.
5. "Entrez Gene: EED embryonic ectoderm development".
6. Cohen AS, Tuysuz B, Shen Y, Bhalla SK, Jones SJ, Gibson WT (Mar 2015). "A novel mutation in EED associated with overgrowth". Journal of Human Genetics. doi:10.1038/jhg.2015.26. PMID 25787343.
7. van der Vlag J, Otte AP (Dec 1999). "Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation". Nat. Genet. 23 (4): 474–8. doi:10.1038/70602. PMID 10581039.
8. van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E (Jun 1998). "Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes". Mol. Cell. Biol. 18 (6): 3572–9. PMC 108938. PMID 9584197.
9. Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K (Oct 1998). "Point mutations in the WD40 domain of Eed block its interaction with Ezh2". Mol. Cell. Biol. 18 (10): 5634–42. PMC 109149. PMID 9742080.
10. Jin Q, van Eynde A, Beullens M, Roy N, Thiel G, Stalmans W, Bollen M (Aug 2003). "The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 (NIPP1), interacts with the polycomb group protein, embryonic ectoderm development (EED), and functions as a transcriptional repressor". J. Biol. Chem. 278 (33): 30677–85. doi:10.1074/jbc.M302273200. PMID 12788942.
11. Enünlü I, Pápai G, Cserpán I, Udvardy A, Jeang KT, Boros I (Sep 2003). "Different isoforms of PRIP-interacting protein with methyltransferase domain/trimethylguanosine synthase localizes to the cytoplasm and nucleus". Biochem. Biophys. Res. Commun. 309 (1): 44–51. doi:10.1016/s0006-291x(03)01514-6. PMID 12943661.

Further reading

• Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.
• Van Maele B, Debyser Z (2005). "HIV-1 integration: an interplay between HIV-1 integrase, cellular and viral proteins". AIDS Rev. 7 (1): 26–43. PMID 15875659.
• Jones CA, Ng J, Peterson AJ, Morgan K, Simon J, Jones RS (1998). "The Drosophila esc and E(z) proteins are direct partners in polycomb group-mediated repression". Mol. Cell. Biol. 18 (5): 2825–34. doi:10.1128/mcb.18.5.2825. PMC 110661. PMID 9566901.
• van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E (1998). "Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes". Mol. Cell. Biol. 18 (6): 3572–9. PMC 108938. PMID 9584197.
• Sewalt RG, van der Vlag J, Gunster MJ, Hamer KM, den Blaauwen JL, Satijn DP, Hendrix T, van Driel R, Otte AP (1998). "Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes". Mol. Cell. Biol. 18 (6): 3586–95. doi:10.1128/mcb.18.6.3586. PMC 108940. PMID 9584199.
• Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K (1998). "Point mutations in the WD40 domain of Eed block its interaction with Ezh2". Mol. Cell. Biol. 18 (10): 5634–42. PMC 109149. PMID 9742080.
• Peytavi R, Hong SS, Gay B, d'Angeac AD, Selig L, Bénichou S, Benarous R, Boulanger P (1999). "HEED, the product of the human homolog of the murine eed gene, binds to the matrix protein of HIV-1". J. Biol. Chem. 274 (3): 1635–45. doi:10.1074/jbc.274.3.1635. PMID 9880543.
• van der Vlag J, Otte AP (1999). "Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation". Nat. Genet. 23 (4): 474–8. doi:10.1038/70602. PMID 10581039.
• Satijn DP, Hamer KM, den Blaauwen J, Otte AP (2001). "The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos". Mol. Cell. Biol. 21 (4): 1360–9. doi:10.1128/MCB.21.4.1360-1369.2001. PMC 99588. PMID 11158321.
• Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D (2002). "Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein". Genes Dev. 16 (22): 2893–905. doi:10.1101/gad.1035902. PMC 187479. PMID 12435631.
• Jin Q, van Eynde A, Beullens M, Roy N, Thiel G, Stalmans W, Bollen M (2003). "The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 (NIPP1), interacts with the polycomb group protein, embryonic ectoderm development (EED), and functions as a transcriptional repressor". J. Biol. Chem. 278 (33): 30677–85. doi:10.1074/jbc.M302273200. PMID 12788942.
• Enünlü I, Pápai G, Cserpán I, Udvardy A, Jeang KT, Boros I (2003). "Different isoforms of PRIP-interacting protein with methyltransferase domain/trimethylguanosine synthase localizes to the cytoplasm and nucleus". Biochem. Biophys. Res. Commun. 309 (1): 44–51. doi:10.1016/S0006-291X(03)01514-6. PMID 12943661.
• Violot S, Hong SS, Rakotobe D, Petit C, Gay B, Moreau K, Billaud G, Priet S, Sire J, Schwartz O, Mouscadet JF, Boulanger P (2003). "The human polycomb group EED protein interacts with the integrase of human immunodeficiency virus type 1". J. Virol. 77 (23): 12507–22. doi:10.1128/JVI.77.23.12507-12522.2003. PMC 262565. PMID 14610174.
• Witte V, Laffert B, Rosorius O, Lischka P, Blume K, Galler G, Stilper A, Willbold D, D'Aloja P, Sixt M, Kolanus J, Ott M, Kolanus W, Schuler G, Baur AS (2004). "HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane". Mol. Cell. 13 (2): 179–90. doi:10.1016/S1097-2765(04)00004-8. PMID 14759364.
• Cao R, Zhang Y (2004). "SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex". Mol. Cell. 15 (1): 57–67. doi:10.1016/j.molcel.2004.06.020. PMID 15225548.
• Pasini D, Bracken AP, Jensen MR, Lazzerini Denchi E, Helin K (2004). "Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity". EMBO J. 23 (20): 4061–71. doi:10.1038/sj.emboj.7600402. PMC 524339. PMID 15385962.