Id: acc0695
Group: 1sens
Protein: EGFR
Gene Symbol: EGFR
Protein Id: P00533
Protein Name: EGFR_HUMAN
PTM: ubiquitination
Site: unclear
Site Sequence:
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: "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 phosphorylation of EGFR mediated by Src kinase activates the downstream signaling pathway and maintains 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 data.

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
- - A B-cell chronic lymphocytic leukemia Phosphorylation 23866081
- - A Lung adenocarcinoma Phosphorylation 23866081
- - A Renal tubulointerstitial fibrosis Ubiquitination 32017279
- - D Gastric adenocarcinoma Glycosylation 30323967
- - D Bladder cancer Ubiquitination 33253711
- - D Osteosarcoma Ubiquitination 32775001
- - D Breast cancer Ubiquitination 31801577
- - D Lung adenocarcinoma Ubiquitination 37240137
- - D Cardiac hypertrophy Ubiquitination 32494592
- - D Thyroid cancer/carcinoma Phosphorylation 16822827
- - P B-cell chronic lymphocytic leukemia Phosphorylation 23866081
- - P Lung adenocarcinoma Phosphorylation 23866081
- - P Epidermoid carcinoma Phosphorylation 23499740
- - P Thyroid cancer/carcinoma Phosphorylation 11299771
- - U Ovarian cancer/carcinoma Phosphorylation 22952709
- - U Head and neck squamous cell carcinoma Phosphorylation 23799848
- - U Colon cancer/carcinoma Phosphorylation 24665413
- - U Breast cancer Ubiquitination 36841821
- - U Hepatocellular carcinoma Ubiquitination 32382041
- - U Gastric cancer Ubiquitination 34034092
- - U Glioma Phosphorylation 24403856
- - U Hepatocellular carcinoma Ubiquitination 33116595
- - U Glioblastoma Ubiquitination 36335869
- - U Non-small cell lung cancer Phosphorylation 36896765
- - U Follicular thyroid carcinoma Glycosylation 32442537
- - U Head and neck squamous cell carcinoma Glycosylation 29930379

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: