PMADS

Id:	acc0739
Group:	2sens
Protein:	ERalpha
Gene Symbol:	ESR1
Protein Id:	P03372
Protein Name:	ESR1_HUMAN
PTM:	methylation
Site:	unclear
Site Sequence:
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:	modulate
Effect Info:	"Tamoxifen stimulates ERalpha methylation by PRMT5 and participates in the inhibition of ERalpha transcriptional activity, thereby suppressing tumor proliferation."
Note:
Score:	4.0
Pubmed(PMID):	37458145
Sentence Index:	37458145_4-5
Sentence:	"Mechanistically, we discovered that tamoxifen stimulates ERalpha methylation by PRMT5, a key event for its binding to corepressors such as SMRT and HDAC1, participating in the inhibition of the transcriptional activity of ERalpha. Although PRMT5 is mainly localized in the cytoplasm of tumor cells, our analyses show that tamoxifen triggers its nuclear translocation in tamoxifen-sensitive tumors but not in resistant ones."

Sequence & Structure:

MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
ESR1	TOREMIFENE CITRATE	Estrogen receptor modulator	4	-	breast carcinoma	DailyMed DailyMed
ESR1	FULVESTRANT	Estrogen receptor antagonist	4	-	breast carcinoma	DailyMed
ESR1	CLOMIPHENE CITRATE	Estrogen receptor alpha modulator	4	-	infertility	DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed
ESR1	CLOMIPHENE CITRATE	Estrogen receptor alpha modulator	4	Completed	infertility	ClinicalTrials ClinicalTrials
ESR1	CLOMIPHENE CITRATE	Estrogen receptor alpha modulator	4	Unknown status	infertility	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
ESR1	DIETHYLSTILBESTROL DIPHOSPHATE	Estrogen receptor agonist	4	-	neoplasm	ATC
ESR1	POLYESTRADIOL PHOSPHATE	Estrogen receptor alpha agonist	4	-	neoplasm	ATC
ESR1	FULVESTRANT	Estrogen receptor antagonist	4	-	neoplasm	ATC
ESR1	ETHINYL ESTRADIOL	Estrogen receptor alpha agonist	4	-	neoplasm	ATC
ESR1	TAMOXIFEN	Estrogen receptor alpha modulator	4	-	neoplasm	ATC
ESR1	DIETHYLSTILBESTROL	Estrogen receptor alpha agonist	4	-	neoplasm	ATC
ESR1	CLOMIPHENE CITRATE	Estrogen receptor alpha modulator	4	-	polycystic ovary syndrome	DailyMed
ESR1	CLOMIPHENE CITRATE	Estrogen receptor alpha modulator	4	Completed	polycystic ovary syndrome	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
ESR1	CLOMIPHENE CITRATE	Estrogen receptor alpha modulator	4	Terminated	polycystic ovary syndrome	ClinicalTrials
ESR1	CLOMIPHENE CITRATE	Estrogen receptor alpha modulator	4	Unknown status	polycystic ovary syndrome	ClinicalTrials ClinicalTrials
ESR1	ESTETROL	Estrogen receptor agonist	4	-	pregnancy	FDA
ESR1	ESTROPIPATE	Estrogen receptor alpha agonist	4	-	osteoporosis	DailyMed
ESR1	ESTROGENS, CONJUGATED	Estrogen receptor agonist	4	-	osteoporosis	DailyMed
ESR1	FULVESTRANT	Estrogen receptor antagonist	4	-	breast neoplasm	EMA
ESR1	FULVESTRANT	Estrogen receptor antagonist	4	Terminated	breast neoplasm	ClinicalTrials
ESR1	ELACESTRANT HYDROCHLORIDE	Estrogen receptor alpha degrader	4	-	breast neoplasm	FDA
ESR1	ESTRADIOL	Estrogen receptor alpha agonist	4	-	osteoporosis	DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed
ESR1	ESTRADIOL	Estrogen receptor alpha agonist	4	-	postmenopausal osteoporosis	DailyMed DailyMed DailyMed
ESR1	LASOFOXIFENE TARTRATE	Estrogen receptor modulator	4	-	postmenopausal osteoporosis	EMA
ESR1	ESTROGENS, CONJUGATED	Estrogen receptor agonist	4	-	postmenopausal osteoporosis	DailyMed DailyMed DailyMed

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 data.

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
-	-	P	Breast cancer/tumor/carcinoma	Ubiquitination	24125069
-	-	P	Breast cancer/tumor/carcinoma	Methylation	2733079
S	-	P	Breast cancer/tumor/carcinoma	Phosphorylation	23946788
S	-	P	Breast cancer/tumor/carcinoma	Phosphorylation	22733972
-	-	P	Breast cancer	Ubiquitination	31518603
-	-	U	Breast cancer	Ubiquitination	32599554
-	-	U	Breast cancer/tumor/carcinoma	Methylation	18647968
-	-	U	Breast cancer	Ubiquitination	36271315
-	-	U	Breast cancer	Ubiquitination	34645792
-	-	U	Breast cancer	Ubiquitination	33771975
-	-	U	Breast cancer	Ubiquitination	34035221
-	-	U	Endometrial cancer	Ubiquitination	36423684
-	-	U	Breast cancer	Ubiquitination	36221793
-	-	U	Breast cancer	Ubiquitination	35392925
-	-	U	Breast cancer	Ubiquitination	32973333
S	-	U	Breast cancer/tumor/carcinoma	Phosphorylation	24051437
-	-	U	Breast cancer/tumor/carcinoma	Methylation	3917730
-	-	U	Breast cancer/tumor/carcinoma	Methylation	24649078

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