PMADS

Id:	acc1160
Group:	2sens
Protein:	HER2
Gene Symbol:	ERBB2
Protein Id:	P04626
Protein Name:	ERBB2_HUMAN
PTM:	phosphorylation
Site:	Tyr1248
Site Sequence:	GTPTAENPEYLGLDVPV----
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:	inhibit
Effect Info:	Metformin reduces tamoxifen resistance by inhibiting the activation of HER2 (Tyr1248)/HER3 (Tyr1289)/Akt (Ser473).
Note:
Score:	5.0
Pubmed(PMID):	26581908
Sentence Index:	26581908_7-8
Sentence:	"Known as a HER3 ligand, heregulin (HRG)-beta1-induced phosphorylation of HER2, HER3 and Akt, and protein interaction of HER2/HER3 and colony formation were inhibited by metformin in both cells. Consistent with the results in the two cell lines, we identified that metformin inhibited HER2/HER3/Akt signaling axis activated by HRG-beta1 using the HER2 and HER3-overexpressing breast cancer cell line SK-BR-3."

Sequence & Structure:

MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNLELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLALTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSANIQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLPDLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTVPWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARCPSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQGGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
ERBB2	LAPATINIB DITOSYLATE	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	breast carcinoma	FDA
ERBB2	TRASTUZUMAB EMTANSINE	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	breast carcinoma	DailyMed
ERBB2	NERATINIB MALEATE	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	breast carcinoma	FDA
ERBB2	TRASTUZUMAB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	breast carcinoma	DailyMed
ERBB2	PERTUZUMAB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	breast carcinoma	DailyMed
ERBB2	TRASTUZUMAB EMTANSINE	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	neoplasm	ATC
ERBB2	PERTUZUMAB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	neoplasm	ATC
ERBB2	TRASTUZUMAB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	neoplasm	ATC
ERBB2	DACOMITINIB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	neoplasm	ATC
ERBB2	VANDETANIB	Epidermal growth factor receptor inhibitor	4	-	neoplasm	ATC
ERBB2	MASOPROCOL	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	neoplasm	ATC
ERBB2	TUCATINIB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	neoplasm	ATC
ERBB2	TRASTUZUMAB DERUXTECAN	Receptor protein-tyrosine kinase erbB-2 binding agent	4	-	neoplasm	ATC
ERBB2	MARGETUXIMAB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	neoplasm	ATC
ERBB2	VANDETANIB	Epidermal growth factor receptor inhibitor	4	-	thyroid carcinoma	DailyMed
ERBB2	AFATINIB DIMALEATE	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	non-small cell lung carcinoma	DailyMed
ERBB2	AFATINIB DIMALEATE	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	Not yet recruiting	non-small cell lung carcinoma	ClinicalTrials
ERBB2	DACOMITINIB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	non-small cell lung carcinoma	EMA FDA
ERBB2	VANDETANIB	Epidermal growth factor receptor inhibitor	4	-	thyroid neoplasm	EMA
ERBB2	TUCATINIB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	breast neoplasm	EMA
ERBB2	TRASTUZUMAB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	breast neoplasm	EMA
ERBB2	TRASTUZUMAB DERUXTECAN	Receptor protein-tyrosine kinase erbB-2 binding agent	4	-	breast neoplasm	EMA
ERBB2	PERTUZUMAB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	breast neoplasm	EMA
ERBB2	TRASTUZUMAB EMTANSINE	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	breast neoplasm	EMA
ERBB2	TRASTUZUMAB	Receptor protein-tyrosine kinase erbB-2 inhibitor	4	-	stomach neoplasm	EMA

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!

ERBB2-Ser1024
Cancer	Intensity
BRCA	-1.458
COAD	0.326
HGSC	-1.737
ccRCC	0.439
GBM	0.747
HNSC	-0.154
LUAD	-0.092
LUSC	-0.142
non_ccRCC	1.669
PDAC	0.402
UCEC

ERBB2-Ser1036
Cancer	Intensity
BRCA	-1.701
COAD	0.425
HGSC	-0.079
ccRCC	0.679
GBM
HNSC
LUAD	0.676
LUSC
non_ccRCC
PDAC
UCEC

ERBB2-Ser1043
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

ERBB2-Ser1048
Cancer	Intensity
BRCA
COAD	-0.715
HGSC
ccRCC
GBM
HNSC	1.143
LUAD	-0.427
LUSC
non_ccRCC
PDAC
UCEC

ERBB2-Ser1053
Cancer	Intensity
BRCA	-2.292
COAD	0.486
HGSC	-0.216
ccRCC	-0.118
GBM
HNSC	-0.023
LUAD	0.714
LUSC	0.21
non_ccRCC	1.37
PDAC	-0.131
UCEC

ERBB2-Ser1070
Cancer	Intensity
BRCA	-1.095
COAD
HGSC	1.334
ccRCC	-0.61
GBM
HNSC	0.523
LUAD	-0.64
LUSC	-0.811
non_ccRCC	1.505
PDAC	-0.207
UCEC

ERBB2-Ser1077
Cancer	Intensity
BRCA
COAD	0.412
HGSC	0.861
ccRCC
GBM
HNSC	0.435
LUAD	-1.091
LUSC
non_ccRCC	0.814
PDAC	-1.431
UCEC

ERBB2-Ser1144
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

ERBB2-Ser673
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

ERBB2-Ser698
Cancer	Intensity
BRCA	-2.285
COAD
HGSC	0.761
ccRCC	0.649
GBM	-0.636
HNSC	-0.065
LUAD	0.085
LUSC	-0.146
non_ccRCC	0.779
PDAC	0.859
UCEC

ERBB2-Ser789
Cancer	Intensity
BRCA	-1.452
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	0.13
LUSC	0.654
non_ccRCC	0.668
PDAC
UCEC

ERBB2-Ser968
Cancer	Intensity
BRCA	-0.294
COAD	0.535
HGSC	-1.27
ccRCC	-0.453
GBM
HNSC	0.084
LUAD	0.316
LUSC	0.857
non_ccRCC	1.685
PDAC	-1.459
UCEC

ERBB2-Thr1030
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	0.707
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

ERBB2-Thr1073
Cancer	Intensity
BRCA
COAD
HGSC	-0.246
ccRCC	1.1
GBM
HNSC
LUAD	-0.854
LUSC
non_ccRCC
PDAC
UCEC

ERBB2-Thr1136
Cancer	Intensity
BRCA	-2.065
COAD	1.532
HGSC	0.275
ccRCC	-0.929
GBM
HNSC	0.484
LUAD	0.051
LUSC	0.357
non_ccRCC	0.297
PDAC	0
UCEC

ERBB2-Thr1210
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

ERBB2-Thr671
Cancer	Intensity
BRCA	-1.385
COAD	0.839
HGSC	-1.437
ccRCC	0.209
GBM	-0.262
HNSC	-0.355
LUAD	0.098
LUSC	1.148
non_ccRCC	1.595
PDAC	-0.449
UCEC

ERBB2-Tyr1109
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

ERBB2-Tyr847
Cancer	Intensity
BRCA
COAD
HGSC	-0.707
ccRCC
GBM
HNSC	0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
Y	1248	D	Breast cancer	Phosphorylation	35505646
Y	1248	D	Head and neck squamous cell carcinoma	Phosphorylation	21281788
Y	1248	D	Non-small cell lung cancer/carcinoma	Phosphorylation	18687633

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