Id: acc0696
Group: 1sens
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: DiFi5
Disease Info:
Drug: cetuximab
Drug Info: "Cetuximab is a recombinant human-mouse chimeric monoclonal antibody that specifically binds to the epidermal growth factor receptor (EGFR), competitively inhibiting ligand binding and blocking downstream signaling pathways, thereby inhibiting cancer cell proliferation, inducing apoptosis, and reducing the production of matrix metalloproteinases and vascular endothelial growth factor; it is used in combination with irinotecan for EGFR-positive, irinotecan-resistant metastatic colorectal cancer, as a monotherapy for patients intolerant to irinotecan, and in combination with radiotherapy for locally advanced head and neck squamous cell carcinoma. "
Effect: inhibit
Effect Info: "The ubiquitination and phosphorylation of EGFR play a crucial role in cetuximab resistance. Ubiquitination leads to the degradation of EGFR, reducing the target sites for cetuximab, while the phosphorylation of EGFR mediated by Src kinase activates the downstream signaling pathway, maintaining the growth and survival of tumor cells."
Note:
Score: 5.0
Pubmed(PMID): 17804738
Sentence Index:
Sentence:

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: