PMADS

Id:	acc1757
Group:	2sens
Protein:	EZH2
Gene Symbol:	EZH2
Protein Id:	Q15910
Protein Name:	EZH2_HUMAN
PTM:	phosphorylation
Site:	Ser21
Site Sequence:	PVCWRKRVKSEYMRLRQLKRF
Disease Category:	Cancer
Disease:	Breast Cancer
Disease Subtype:
Disease Cellline:	MCF7
Disease Info:
Drug:	tamoxifen
Drug Info:	"Tamoxifen is a selective estrogen receptor modulator (SERM) used primarily for the treatment of estrogen receptor-positive breast cancer in women, including adjuvant therapy, advanced cases, and recurrent disease, by competitively inhibiting estrogen binding to its receptor and suppressing cancer cell proliferation."
Effect:	resist
Effect Info:	"Long-term use of Genistein (GE) leads to phosphorylation of EZH2, which affects the final increase in HER2 expression through ERK1/2, thereby resulting in tamoxifen resistance."
Note:
Score:	5.0
Pubmed(PMID):	36356296
Sentence Index:	36356296_9-10
Sentence:	"We identified a novel pathway by which EZH2 phosphorylation contributed to long-term low-level GE-induced HER2 overexpression, and provided new insight for long-term low-level GE-induced acquired endocrine resistance. For breast cancer patients, long-term low-level use of soy supplements has potential health risks, and monitoring dietary exposure to GE is advisable when patients are treated with tamoxifen."

Sequence & Structure:

MGQTGKKSEKGPVCWRKRVKSEYMRLRQLKRFRRADEVKSMFSSNRQKILERTEILNQEWKQRRIQPVHILTSVSSLRGTRECSVTSDLDFPTQVIPLKTLNAVASVPIMYSWSPLQQNFMVEDETVLHNIPYMGDEVLDQDGTFIEELIKNYDGKVHGDRECGFINDEIFVELVNALGQYNDDDDDDDGDDPEEREEKQKDLEDHRDDKESRPPRKFPSDKIFEAISSMFPDKGTAEELKEKYKELTEQQLPGALPPECTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFLHPFHATPNTYKRKNTETALDNKPCGPQCYQHLEGAKEFAAALTAERIKTPPKRPGGRRRGRLPNNSSRPSTPTINVLESKDTDSDREAGTETGGENNDKEEEEKKDETSSSSEANSRCQTPIKMKPNIEPPENVEWSGAEASMFRVLIGTYYDNFCAIARLIGTKTCRQVYEFRVKESSIIAPAPAEDVDTPPRKKKRKHRLWAAHCRKIQLKKDGSSNHVYNYQPCDHPRQPCDSSCPCVIAQNFCEKFCQCSSECQNRFPGCRCKAQCNTKQCPCYLAVRECDPDLCLTCGAADHWDSKNVSCKNCSIQRGSKKHLLLAPSDVAGWGIFIKDPVQKNEFISEYCGEIISQDEADRRGKVYDKYMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIGIFAKRAIQTGEELFFDYRYSQADALKYVGIEREMEIP

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	4	-	neoplasm	ATC
EZH2	TAZEMETOSTAT HYDROBROMIDE	Histone-lysine N-methyltransferase EZH2 inhibitor	4	-	sarcoma	FDA
EZH2	TAZEMETOSTAT HYDROBROMIDE	Histone-lysine N-methyltransferase EZH2 inhibitor	4	-	follicular lymphoma	DailyMed
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	3	Recruiting	epithelioid sarcoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	3	Recruiting	follicular lymphoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	2	Not yet recruiting	neoplasm of mature B-cells	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	2	Completed	neoplasm of mature B-cells	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	2	Recruiting	lymphoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	2	Recruiting	neoplasm	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	2	Completed	mesothelioma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	2	Recruiting	follicular lymphoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	2	Terminated	follicular lymphoma	ClinicalTrials ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	2	Not yet recruiting	nasal cavity and paranasal sinus carcinoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Terminated	head and neck squamous cell carcinoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Completed	neoplasm of mature B-cells	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Active, not recruiting	metastatic prostate cancer	ClinicalTrials ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Recruiting	acute myeloid leukemia	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Active, not recruiting	diffuse large B-cell lymphoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Recruiting	diffuse large B-cell lymphoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Completed	lymphoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Not yet recruiting	lymphoma	ClinicalTrials
EZH2	GSK2816126	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Terminated	neoplasm	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Recruiting	small cell lung carcinoma	ClinicalTrials
EZH2	TAZEMETOSTAT HYDROBROMIDE	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Recruiting	small cell lung carcinoma	ClinicalTrials
EZH2	TAZEMETOSTAT	Histone-lysine N-methyltransferase EZH2 inhibitor	1	Recruiting	multiple myeloma	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

EZH2-Ser362
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	-0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.707

EZH2-Ser363
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	-0.707
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC

EZH2-Ser366
Cancer	Intensity
BRCA	-0.692
COAD	-0.307
HGSC	1.932
ccRCC
GBM
HNSC	-0.815
LUAD	-0.165
LUSC
non_ccRCC
PDAC
UCEC	0.047

EZH2-Ser380
Cancer	Intensity
BRCA
COAD	-0.954
HGSC
ccRCC
GBM	-0.483
HNSC
LUAD	1.304
LUSC	-1.153
non_ccRCC
PDAC	0.63
UCEC	0.657

EZH2-Ser405
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	-0.707
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC

EZH2-Ser412
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC	-0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EZH2-Ser475
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.707
GBM
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

EZH2-Thr345
Cancer	Intensity
BRCA
COAD	0.756
HGSC
ccRCC	0.377
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC	-1.134
UCEC

EZH2-Thr367
Cancer	Intensity
BRCA	-0.141
COAD	-0.53
HGSC	1.254
ccRCC
GBM
HNSC
LUAD	0.402
LUSC	-1.606
non_ccRCC
PDAC
UCEC	0.621

EZH2-Thr386
Cancer	Intensity
BRCA
COAD	0.707
HGSC
ccRCC
GBM
HNSC	-0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EZH2-Thr388
Cancer	Intensity
BRCA
COAD	0.707
HGSC
ccRCC
GBM
HNSC	-0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EZH2-Thr487
Cancer	Intensity
BRCA	-1.233
COAD	0.478
HGSC	-0.487
ccRCC	1.474
GBM	0.933
HNSC	1.026
LUAD	-1.498
LUSC	-0.846
non_ccRCC	-0.72
PDAC	0.259
UCEC	0.613

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	21	U	HER2-positive breast cancer	Phosphorylation	37803297
S	21	U	Melanoma	Phosphorylation	26517694
S	21	U	Prostate cancer	Phosphorylation	34230470

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb