PMADS

Id:	acc0807
Group:	2sens
Protein:	HER2
Gene Symbol:	ERBB2
Protein Id:	P04626
Protein Name:	ERBB2_HUMAN
PTM:	phosphorylation
Site:	Tyr1222
Site Sequence:	FSPAFDNLYYWDQDPPERGAP
Disease Category:	Cancer
Disease:	Breast Cancer
Disease Subtype:
Disease Cellline:	HCC1954
Disease Info:
Drug:	AZD5363
Drug Info:	"Capivasertib (AZD5363) is an orally active pan-AKT kinase inhibitor that inhibits Akt1, Akt2, and Akt3 with IC50 values of 3, 7, and 7 nM, respectively."
Effect:	inhibit
Effect Info:	"The addition of AZD8931 blocked the HER2/HER3 phosphorylation induced by AZD5363, and led to the concomitant inhibition of the PI3K/AKT/mTOR and ERK signaling pathways and the induction of apoptosis, thereby enhancing the activity of AZD5363 in HER2 - amplified breast cancer cells."
Note:
Score:	5.0
Pubmed(PMID):	26095475
Sentence Index:	26095475_5-6
Sentence:	"Investigation of the mechanism by western blot analysis revealed that the addition of AZD8931 prevented the induction of HER2/HER3 phosphorylation induced by AZD5363 and resulted in concomitant inhibition of both the PI3K/AKT/mTOR and ERK signalling pathways and induction of apoptosis. Using the HCC1954 xenograft model, which is resistant to trastuzumab, we show that the combination of AZD5363 and AZD8931 is more efficacious than either agent alone, resulting in profound tumour regressions."

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	1222	U	Breast cancer	Phosphorylation	19239686

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