CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012652
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
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
39FRRADEVKSMFSSNRubiquitination[1]
61EILNQEWKQRRIQPVubiquitination[1, 2]
477QVYEFRVKESSIIAPubiquitination[1]
574CKAQCNTKQCPCYLAubiquitination[1]
602AADHWDSKNVSCKNCubiquitination[1]
607DSKNVSCKNCSIQRGubiquitination[1]
634AGWGIFIKDPVQKNEubiquitination[1]
740YSQADALKYVGIEREubiquitination[2]
Reference
 [1] 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]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
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
MGQTGKKSEK GPVCWRKRVK SEYMRLRQLK RFRRADEVKS MFSSNRQKIL ERTEILNQEW 60
KQRRIQPVHI LTSVSSLRGT RECSVTSDLD FPTQVIPLKT LNAVASVPIM YSWSPLQQNF 120
MVEDETVLHN IPYMGDEVLD QDGTFIEELI KNYDGKVHGD RECGFINDEI FVELVNALGQ 180
YNDDDDDDDG DDPEEREEKQ KDLEDHRDDK ESRPPRKFPS DKIFEAISSM FPDKGTAEEL 240
KEKYKELTEQ QLPGALPPEC TPNIDGPNAK SVQREQSLHS FHTLFCRRCF KYDCFLHRKC 300
NYSFHATPNT YKRKNTETAL DNKPCGPQCY QHLEGAKEFA AALTAERIKT PPKRPGGRRR 360
GRLPNNSSRP STPTINVLES KDTDSDREAG TETGGENNDK EEEEKKDETS SSSEANSRCQ 420
TPIKMKPNIE PPENVEWSGA EASMFRVLIG TYYDNFCAIA RLIGTKTCRQ VYEFRVKESS 480
IIAPAPAEDV DTPPRKKKRK HRLWAAHCRK IQLKKDGSSN HVYNYQPCDH PRQPCDSSCP 540
CVIAQNFCEK FCQCSSECQN RFPGCRCKAQ CNTKQCPCYL AVRECDPDLC LTCGAADHWD 600
SKNVSCKNCS IQRGSKKHLL LAPSDVAGWG IFIKDPVQKN EFISEYCGEI ISQDEADRRG 660
KVYDKYMCSF LFNLNNDFVV DATRKGNKIR FANHSVNPNC YAKVMMVNGD HRIGIFAKRA 720
IQTGEELFFD YRYSQADALK YVGIEREMEI P 751 
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