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Protein Page:
EZH2 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
EZH2 a histone H3 Lys 27 (H3K27) methyltransferase and Polycomb group protein with oncogenic activity. A master regulatory protein that plays a critical role in development. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates K9 and K27 of histone H3, leading to transcriptional repression of the affected target genes. PRC2 includes the Ezh2, EED, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The recruitment of PRC2 to a promoter leads to increased levels of di- and trimethylation of H3K27 (H3K27me2/3), regulating the balance between self-renewal and differentiation of embryonic stem cells (ESCs). The recruitment of PRC2 to promoters in ES cells is interdependent on Jarid 2. ESCs lacking the PRC2 component EED are deficient in Jarid2 promoter activity, while the knockdown of Jarid 2 reduces PRC2 at its target promoters. Able to mono-, di- and trimethylate K27 of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, p14ARF and retinoic acid target genes. Binds ATRX via the SET domain. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with HDAC1 and HDAC2. Interacts with PRAME. Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis. Expression decreases during senescence of embryonic fibroblasts. Expression peaks at the G1/S phase boundary. Expression is induced by E2F1, E2F2 and E2F3. Expression is reduced in cells subject to numerous types of stress including UV-, IR- and bleomycin-induced DNA damage and by activation of p53. It has been reported that phosphorylation by AKT1 on S21 reduces methyltransferase activity. Note: This description may include information from UniProtKB.
Protein type: Methyltransferase; EC 2.1.1.43; Methyltransferase, protein lysine; Oncoprotein
Cellular Component: nucleoplasm; ESC/E(Z) complex; pronucleus; nuclear chromatin; cytoplasm; nucleolus; nucleus
Molecular Function: histone methyltransferase activity; protein binding; DNA binding; chromatin DNA binding; RNA binding; sequence-specific DNA binding; chromatin binding; histone lysine N-methyltransferase activity (H3-K27 specific)
Biological Process: negative regulation of striated muscle cell differentiation; establishment and/or maintenance of chromatin architecture; transcription, DNA-dependent; regulation of gliogenesis; negative regulation of transcription from RNA polymerase II promoter; regulation of cell proliferation; negative regulation of retinoic acid receptor signaling pathway; positive regulation of MAP kinase activity; cerebellar cortex development; positive regulation of Ras GTPase activity; regulation of transcription, DNA-dependent; negative regulation of gene expression, epigenetic; negative regulation of epidermal cell differentiation; negative regulation of transcription, DNA-dependent
Reference #:  Q15910 (UniProtKB)
Alt. Names/Synonyms: enhancer of zeste 2; Enhancer of zeste homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX-1; ENX1; EZH1; EZH2; Histone-lysine N-methyltransferase EZH2; KMT6; KMT6A; Lysine N-methyltransferase 6; MGC9169
Gene Symbols: EZH2
Molecular weight: 85,363 Da
Basal Isoelectric point: 6.65  Predict pI for various phosphorylation states
CST Pathways:  Histone Methylation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

EZH2

Protein Structure Not Found.


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Sites Implicated In
carcinogenesis, altered: T345‑p
cell growth, altered: T345‑p
cell growth, induced: T345‑p, T487‑p
cell motility, altered: T345‑p
transcription, altered: T345‑p
enzymatic activity, inhibited: S21‑p
molecular association, regulation: S21‑p, Y641‑p
protein degradation: T345‑p, T487‑p
protein stabilization: Y641‑p
ubiquitination: T345‑p, T487‑p, Y641‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 1 S8-p MGQTGKKsEKGPVCW
1 1 S21-p CWRKRVKsEyMRLRQ
0 1 Y23-p RKRVKsEyMRLRQLK
0 1 K61-ub EILNQEWkQRRIQPV
0 1 S76-p HILTSVSsLRGTREC
1 0 S76-gl HILTSVSsLRGTREC
0 1 S220-p RPPRKFPsDKIFEAI
0 2 T302-p FLHPFHAtPNTYKRK
0 1 K309 tPNTYKRKNTETALD
0 5 T339-p KEFAAALtAERIKtP
4 7 T345-p LtAERIKtPPKRPGG
0 10 S362-p RGRLPNNssRPstPt
0 33 S363-p GRLPNNssRPstPtI
0 29 S366-p PNNssRPstPtINVL
1 50 T367-p NNssRPstPtINVLE
0 10 T369-p ssRPstPtINVLEsK
0 1 N371 RPstPtINVLEsKDT
0 1 S375-p PtINVLEsKDTDsDR
0 5 S380-p LEsKDTDsDREAGTE
0 1 T388-p DREAGTEtGGENNDK
0 1 S405-p EEKKDETssSsEANs
0 3 S406-p EKKDETssSsEANsR
0 1 S408-p KDETssSsEANsRCQ
0 5 S412-p ssSsEANsRCQtPIK
1 7 T416-p EANsRCQtPIKMKPN
0 1 T460-p AIARLIGtKTCRQVY
3 87 T487-p APAEDVDtPPRKKKR
0 2 K505-m2 LWAAHCRkIQLkkDG
0 1 K509-m2 HCRkIQLkkDGSSNH
0 2 K510-m2 CRkIQLkkDGSSNHV
0 1 T568 RCKAQCNTKQCPCYL
1 0 Y641-p KNEFISEyCGEIISQ
1 0 S647 EyCGEIISQDEADRR
0 1 Y696-p HSVNPNCyAKVMMVN
1 0 S729 LFFDYRYSQADALKY
  EZH2 iso2  
S8 MGQTGKKSEKGPVCW
S21 CWRKRVKSEYMRLRQ
Y23 RKRVKSEYMRLRQLK
K61 EILNQEWKQRRIQPV
S76 HILTSVSSLRGTREC
S76 HILTSVSSLRGTREC
S220 RPPRKFPSDKIFEAI
T307 CNYSFHATPNTYKRK
K314 TPNTYKRKNTETALD
T344 KEFAAALTAERIKTP
T350 LTAERIKTPPKRPGG
S367 RGRLPNNSSRPSTPT
S368 GRLPNNSSRPSTPTI
S371 PNNSSRPSTPTINVL
T372 NNSSRPSTPTINVLE
T374 SSRPSTPTINVLESK
N376 RPSTPTINVLESKDT
S380 PTINVLESKDTDSDR
S385 LESKDTDSDREAGTE
T393 DREAGTETGGENNDK
S410 EEKKDETSSSSEANS
S411 EKKDETSSSSEANSR
S413 KDETSSSSEANSRCQ
S417 SSSSEANSRCQTPIK
T421 EANSRCQTPIKMKPN
T465 AIARLIGTKTCRQVY
T492 APAEDVDTPPRKKKR
K510 LWAAHCRKIQLKKDG
K514 HCRKIQLKKDGSSNH
K515 CRKIQLKKDGSSNHV
T573 RCKAQCNTKQCPCYL
Y646 KNEFISEYCGEIIsQ
S652-p EYCGEIIsQDEADRR
Y701 HSVNPNCYAKVMMVN
S734-p LFFDYRYsQADALKY
  mouse

 
S8 MGQTGKKSEKGPVCW
S21 CWRKRVKSEYMRLRQ
Y23 RKRVKSEYMRLRQLK
K61 ETLNQEWKQRRIQPV
S76 HIMTSVSSLRGTREC
S76 HIMTSVSSLRGTREC
A220 CPPRKFPADKIFEAI
T302 FLHPFHATPNTYKRk
K309-ac TPNTYKRkNTETALD
T339-p KEFAAALtAERIKtP
T345-p LtAERIKtPPKRPGG
S362-p RGRLPNNssRPstPt
S363-p GRLPNNssRPstPtI
S366-p PNNssRPstPtISVL
T367-p NNssRPstPtISVLE
T369-p ssRPstPtISVLESK
S371 RPstPtISVLESKDT
S375 PtISVLESKDTDSDR
S380 LESKDTDSDREAGTE
T388 DREAGTETGGENNDK
S405 EEKKDETSSSSEANS
S406 EKKDETSSSSEANSR
S408 KDETSSSSEANSRCQ
S412 SSSSEANSRCQTPIK
T416 EANSRCQTPIKMKPN
T460 AIARLIGTKTCRQVY
T487-p VPTEDVDtPPRKKKR
K505 LWAAHCRKIQLKKDG
K509 HCRKIQLKKDGSSNH
K510 CRKIQLKKDGSSNHV
T568-p RCKAQCNtKQCPCYL
Y641 KNEFISEYCGEIISQ
S647 EYCGEIISQDEADRR
Y696 HSVNPNCYAKVMMVN
S729 LFFDYRYSQADALKY
  rat

 
S8 MGQTGKKSEKGPVCW
S21 CWRKRVKSEYMRLRQ
Y23 RKRVKSEYMRLRQLK
K61 ETLNQEWKQRRIQPV
S76 HIMTSVSSLRGTREC
S76 HIMTSVSSLRGTREC
A220 CPPRKFPADKIFEAI
T302 FLHPFHATPNTYKRK
K309 TPNTYKRKNTETALD
T339 KEFAAALTAERIKTP
T345 LTAERIKTPPKRPGG
S362 RGRLPNNSsRPStPt
S363-p GRLPNNSsRPStPtI
S366 PNNSsRPStPtIsVL
T367-p NNSsRPStPtIsVLE
T369-p SsRPStPtIsVLESK
S371-p RPStPtIsVLESKDT
S375 PtIsVLESKDTDsDR
S380-p LESKDTDsDREAGTE
T388 DREAGTETGGENNDK
S405 EEKKDETSSSSEANS
S406 EKKDETSSSSEANSR
S408 KDETSSSSEANSRCQ
S412 SSSSEANSRCQTPIK
T416 EANSRCQTPIKMKPN
T460 AIARLIGTKTCRQVY
T487-p VPTEDVDtPPRKKKR
K505 LWAAHCRKIQLKKDG
K509 HCRKIQLKKDGSSNH
K510 CRKIQLKKDGSSNHV
T568 RCKAQCNTKQCPCYL
Y641 KNEFISEYCGEIISQ
S647 EYCGEIISQDEADRR
Y696 HSVNPNCYAKVMMVN
S729 LFFDYRYSQADALKY
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