UniProt Accession

 EZH2_HUMAN; Q15910; B2RAQ1; B3KS30; B7Z1D6; B7Z7L6; Q15755; Q75MG3; Q92857; Q96FI6 

Genbank Protein ID

 X95653; U61145; AK302216; AK092676; AK293239; AK314291; AC006323; AC073140; CH471146; CH471146; BC010858; U52965 

Genbank Nucleotide ID

 CAA64955.1; AAC51520.1; BAH13652.1; BAG52592.1; BAH11472.1; BAG36948.1; AAS07448.1; EAW80067.1; EAW80070.1; AAH10858.1; AAC50591.1 

Protein Name

 Histone-lysine N-methyltransferase EZH2 

Protein Synonyms/Alias

 ENX-1; Enhancer of zeste homolog 2; Lysine N-methyltransferase 6 

Gene Name

 EZH2 

Gene Synonyms/Alias

 KMT6 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
61	EILNQEWKQRRIQPV	ubiquitination	[1]
461	IARLIGTKTCRQVYE	ubiquitination	[2]
472	QVYEFRVKESSIIAP	ubiquitination	[3, 4]
569	CKAQCNTKQCPCYLA	ubiquitination	[2, 4, 5]
597	AADHWDSKNVSCKNC	ubiquitination	[4]
602	DSKNVSCKNCSIQRG	ubiquitination	[4]
629	AGWGIFIKDPVQKNE	ubiquitination	[4]
713	HRIGIFAKRAIQTGE	ubiquitination	[4]
735	YSQADALKYVGIERE	ubiquitination	[1, 2, 3, 4]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys- 27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Compared to EZH2-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. 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, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4. 

Sequence Annotation

 DOMAIN 503 605 CXC.
 DOMAIN 612 727 SET.
 REGION 1 340 Interaction with DNMT1, DNMT3A and
 REGION 39 68 Interaction with EED (By similarity).
 MOD_RES 21 21 Phosphoserine; by PKB/AKT1.
 MOD_RES 345 345 Phosphothreonine; by CDK1 and CDK2.
 MOD_RES 366 366 Phosphoserine.
 MOD_RES 367 367 Phosphothreonine.
 MOD_RES 487 487 Phosphothreonine.  

Keyword

 3D-structure; Alternative splicing; Chromatin regulator; Complete proteome; Disease mutation; Methyltransferase; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repressor; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 746 AA 

Protein Sequence

Gene Ontology

 GO:0035098; C:ESC/E(Z) complex; IDA:UniProtKB.
 GO:0045120; C:pronucleus; IEA:Compara.
 GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO:0001047; F:core promoter binding; IEA:Compara.
 GO:0003677; F:DNA binding; TAS:ProtInc.
 GO:0042054; F:histone methyltransferase activity; IDA:MGI.
 GO:0018024; F:histone-lysine N-methyltransferase activity; IEA:EC.
 GO:0043565; F:sequence-specific DNA binding; IEA:Compara.
 GO:0021695; P:cerebellar cortex development; IEA:Compara.
 GO:0070314; P:G1 to G0 transition; IEA:Compara.
 GO:0070734; P:histone H3-K27 methylation; IEA:Compara.
 GO:0045605; P:negative regulation of epidermal cell differentiation; IEA:Compara.
 GO:0045814; P:negative regulation of gene expression, epigenetic; IDA:UniProtKB.
 GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IMP:UniProtKB.
 GO:0051154; P:negative regulation of striated muscle cell differentiation; IEA:Compara.
 GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IEA:Compara.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
 GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
 GO:0032320; P:positive regulation of Ras GTPase activity; IDA:UniProtKB.
 GO:0042127; P:regulation of cell proliferation; IEA:Compara.
 GO:0014013; P:regulation of gliogenesis; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 

Interpro

 IPR026489; CXC_dom.
 IPR021654; EZH2_WD-Binding.
 IPR001005; SANT/Myb.
 IPR001214; SET_dom. 

Pfam

 PF11616; EZH2_WD-Binding
 PF00856; SET 

SMART

 SM00717; SANT
 SM00317; SET 

PROSITE

 PS51633; CXC
 PS50280; SET 

PRINTS