PMADS

Id:	acc1628
Group:	2sens_supp
Protein:	EGFR
Gene Symbol:	EGFR
Protein Id:	P00533
Protein Name:	EGFR_HUMAN
PTM:	phosphorylation
Site:	Tyr1068
Site Sequence:	PIKEDSFLQRYSSDPTGALTE
Disease Category:	Cancer
Disease:	Lung Cancer
Disease Subtype:	NSCLC
Disease Cellline:	CL1-5
Disease Info:
Drug:	gefitinib
Drug Info:	Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used for the treatment of metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.
Effect:	inhibit
Effect Info:	"Curcumin enhances the antitumor activity of gefitinib in NSCLC cell lines and xenograft mouse models by inhibiting proliferation, down - regulating EGFR phosphorylation, and inducing EGFR ubiquitination and apoptosis."
Note:
Score:	5.0
Pubmed(PMID):	21858220
Sentence Index:	21858220_3-4
Sentence:	"Here, we showed that curcumin can improve the efficiency of gefitinib in the resistant NSCLC cells both in vitro and in vivo models. METHODS/PRINCIPAL FINDINGS: After screening 598 herbal and natural compounds, we found curcumin could inhibit cell proliferation in different gefitinib-resistant NSCLC cell lines; concentration-dependently down-regulate EGFR phosphorylation through promoting EGFR degradation in NSCLC cell lines with wild-type EGFR or T790M EGFR. Curcumin potentiates antitumor activity of gefitinib in cell lines and xenograft mice model of NSCLC through inhibition of proliferation, EGFR phosphorylation, and induction EGFR ubiquitination and apoptosis."

Sequence & Structure:

MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLNTVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRVAPQSSEFIGA

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
EGFR	LAPATINIB DITOSYLATE	Epidermal growth factor receptor erbB1 inhibitor	4	-	breast carcinoma	FDA
EGFR	NERATINIB MALEATE	Epidermal growth factor receptor erbB1 inhibitor	4	-	breast carcinoma	FDA
EGFR	CETUXIMAB	Epidermal growth factor receptor erbB1 inhibitor	4	-	colorectal adenocarcinoma	DailyMed
EGFR	PANITUMUMAB	Epidermal growth factor receptor erbB1 inhibitor	4	-	colorectal adenocarcinoma	DailyMed
EGFR	NECITUMUMAB	Epidermal growth factor receptor erbB1 inhibitor	4	-	neoplasm	ATC
EGFR	AMIVANTAMAB	Epidermal growth factor receptor inhibitor	4	-	neoplasm	ATC
EGFR	CETUXIMAB	Epidermal growth factor receptor erbB1 inhibitor	4	-	neoplasm	ATC
EGFR	CETUXIMAB	Epidermal growth factor receptor erbB1 inhibitor	4	Recruiting	neoplasm	ClinicalTrials
EGFR	VANDETANIB	Epidermal growth factor receptor inhibitor	4	-	neoplasm	ATC
EGFR	PANITUMUMAB	Epidermal growth factor receptor erbB1 inhibitor	4	-	neoplasm	ATC
EGFR	GEFITINIB	Epidermal growth factor receptor erbB1 inhibitor	4	-	neoplasm	ATC
EGFR	DACOMITINIB	Epidermal growth factor receptor erbB1 inhibitor	4	-	neoplasm	ATC
EGFR	MOBOCERTINIB	Epidermal growth factor receptor erbB1 inhibitor	4	-	neoplasm	ATC
EGFR	OSIMERTINIB	Epidermal growth factor receptor erbB1 inhibitor	4	-	neoplasm	ATC
EGFR	BRIGATINIB	Epidermal growth factor receptor erbB1 inhibitor	4	-	neoplasm	ATC
EGFR	CETUXIMAB	Epidermal growth factor receptor erbB1 inhibitor	4	-	squamous cell carcinoma	DailyMed
EGFR	VANDETANIB	Epidermal growth factor receptor inhibitor	4	-	thyroid carcinoma	DailyMed
EGFR	NECITUMUMAB	Epidermal growth factor receptor erbB1 inhibitor	4	-	non-small cell lung carcinoma	EMA DailyMed
EGFR	AFATINIB DIMALEATE	Epidermal growth factor receptor erbB1 inhibitor	4	-	non-small cell lung carcinoma	DailyMed
EGFR	AFATINIB DIMALEATE	Epidermal growth factor receptor erbB1 inhibitor	4	Not yet recruiting	non-small cell lung carcinoma	ClinicalTrials
EGFR	DACOMITINIB	Epidermal growth factor receptor erbB1 inhibitor	4	-	non-small cell lung carcinoma	FDA EMA
EGFR	OSIMERTINIB MESYLATE	Epidermal growth factor receptor erbB1 inhibitor	4	-	non-small cell lung carcinoma	EMA DailyMed
EGFR	ERLOTINIB HYDROCHLORIDE	Epidermal growth factor receptor erbB1 inhibitor	4	-	non-small cell lung carcinoma	DailyMed
EGFR	BRIGATINIB	Epidermal growth factor receptor erbB1 inhibitor	4	-	non-small cell lung carcinoma	EMA FDA
EGFR	AMIVANTAMAB	Epidermal growth factor receptor inhibitor	4	-	non-small cell lung carcinoma	EMA FDA

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!

EGFR-Ser1012
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.224
GBM
HNSC
LUAD	1.093
LUSC	-0.869
non_ccRCC
PDAC
UCEC

EGFR-Ser1019
Cancer	Intensity
BRCA	-0.162
COAD	0.525
HGSC	1.91
ccRCC	-0.216
GBM
HNSC
LUAD	-1.07
LUSC	-1.597
non_ccRCC	-0.132
PDAC	0.291
UCEC	0.453

EGFR-Ser1026
Cancer	Intensity
BRCA
COAD	0.707
HGSC
ccRCC
GBM
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

EGFR-Ser1121
Cancer	Intensity
BRCA
COAD	0.33
HGSC	0.793
ccRCC	-1.123
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EGFR-Ser650
Cancer	Intensity
BRCA
COAD	-0.529
HGSC	1.453
ccRCC	-0.792
GBM
HNSC
LUAD	-1.019
LUSC	-0.082
non_ccRCC
PDAC
UCEC	0.969

EGFR-Ser675
Cancer	Intensity
BRCA	-2.294
COAD
HGSC	0.643
ccRCC	0.535
GBM
HNSC
LUAD	-0.009
LUSC	-0.232
non_ccRCC	0.66
PDAC	0.738
UCEC	-0.041

EGFR-Ser946
Cancer	Intensity
BRCA	0.751
COAD	0.597
HGSC	1.404
ccRCC	-0.059
GBM
HNSC
LUAD	0.114
LUSC	-0.811
non_ccRCC	-2.003
PDAC	0.462
UCEC	-0.456

EGFR-Ser991
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.707
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EGFR-Ser992
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM
HNSC	0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EGFR-Ser994
Cancer	Intensity
BRCA
COAD	0.623
HGSC	-0.784
ccRCC	-0.58
GBM
HNSC
LUAD	-0.129
LUSC
non_ccRCC	-1.376
PDAC	0.785
UCEC	1.461

EGFR-Ser997
Cancer	Intensity
BRCA	1.611
COAD	0.359
HGSC	-2.065
ccRCC	-0.131
GBM
HNSC
LUAD	0.009
LUSC	-0.098
non_ccRCC	0.862
PDAC	-0.488
UCEC	-0.059

EGFR-Thr648
Cancer	Intensity
BRCA	1.108
COAD	0.434
HGSC	1.068
ccRCC	0.044
GBM
HNSC
LUAD	0.416
LUSC	-1.175
non_ccRCC	-1.717
PDAC	-0.77
UCEC	0.592

EGFR-Thr948
Cancer	Intensity
BRCA
COAD	0.914
HGSC	0.483
ccRCC	-0.006
GBM
HNSC
LUAD	-1.39
LUSC
non_ccRCC
PDAC
UCEC

EGFR-Thr996
Cancer	Intensity
BRCA	1.232
COAD	-0.247
HGSC
ccRCC	-1.249
GBM
HNSC
LUAD	-0.683
LUSC	-0.608
non_ccRCC	1.709
PDAC	-0.291
UCEC	0.136

EGFR-Tyr1047
Cancer	Intensity
BRCA
COAD	0.614
HGSC
ccRCC	0.139
GBM
HNSC
LUAD	-0.763
LUSC	-1.224
non_ccRCC
PDAC
UCEC	1.234

EGFR-Tyr1127
Cancer	Intensity
BRCA	0.853
COAD	0.567
HGSC	1.203
ccRCC	-0.756
GBM
HNSC
LUAD	-0.922
LUSC	-0.649
non_ccRCC	-1.614
PDAC	0.354
UCEC	0.964

EGFR-Tyr1152
Cancer	Intensity
BRCA	0.302
COAD	0.15
HGSC	0.898
ccRCC	-0.139
GBM
HNSC
LUAD	-0.637
LUSC	-1.754
non_ccRCC	-0.871
PDAC	0.427
UCEC	1.624

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
Y	1068	D	Glioblastoma multiforme	Phosphorylation	35915159
Y	1068	P	Gastric cancer	Phosphorylation	23613900
Y	1068	P	Tonsillar cancer	Phosphorylation	23564800
Y	1068	U	Non-small cell lung cancer/carcinoma	Phosphorylation	22901364 ; 18687633
Y	1068	U	Prostate cancer/carcinoma/adenocarcinoma	Phosphorylation	22307624
Y	1068	U	Squamous cell carcinoma	Phosphorylation	37109043
Y	1068	U	Pancreatic cancer	Phosphorylation	31851779

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