PMADS

Id:	acc0927
Group:	2sens
Protein:	EGFR
Gene Symbol:	EGFR
Protein Id:	P00533
Protein Name:	EGFR_HUMAN
PTM:	phosphorylation
Site:	Tyr845
Site Sequence:	RDLAARNVLVKTPQHVKITDF
Disease Category:	Cancer
Disease:	Colorectal Cancer
Disease Subtype:
Disease Cellline:	HT29
Disease Info:
Drug:	DCA
Drug Info:	"Deoxycholic acid (DCA): A secondary bile acid utilized as a pharmaceutical agent for localized fat reduction through adipocyte cytolysis, commonly employed in submental contouring. "
Effect:	modulate
Effect Info:	"Treatment of human colon cancer cells with DCA leads to the phosphorylation of p-CAMKII and EGFR at the c-Src-dependent phosphorylation site Tyr84. Subsequently, this activation mediates the downstream activity of MAPK and the subsequent phosphorylation of ERK1/2, thereby promoting tumorigenesis."
Note:
Score:	4.0
Pubmed(PMID):	27086143
Sentence Index:	27086143_7-8
Sentence:	"Further evaluation showed that DCA treatment increased intracellular calcium levels and CAMKII phosphorylation, and that blocking calcium with BAPTA-AM abrogated MAPK activation induced by DCA, but not by EGF. Finally we showed that DCA-induced CAMKII leads to MAPK activation through the recruitment of c-Src. Taken together, we demonstrated that DCA regulates MAPK activation through calcium signaling, an alternative mechanism not previously recognized in human colon cancer cells."

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	845	P	Lung adenocarcinoma	Phosphorylation	23866081
Y	845	U	Liver cancer	Phosphorylation	23220047
Y	845	U	Squamous cell carcinoma	Phosphorylation	37109043
Y	845	U	Non-small cell large cell lung carcinoma	Phosphorylation	16505275 ; 16505275
Y	845	U	Breast cancer/tumor/carcinoma	Phosphorylation	22179831 ; 23066441
Y	845	U	Hepatocellular carcinoma	Phosphorylation	16936701
Y	845	U	Non-small cell squamous cell lung carcinoma	Phosphorylation	16505275 ; 16505275

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