Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTG96HZ)

DTT Name EGFR messenger RNA (EGFR mRNA)
Synonyms Receptor tyrosine-protein kinase erbB-1 (mRNA); Proto-oncogene c-ErbB-1 (mRNA); HER1 (mRNA); Epidermal growth factor receptor (mRNA); ERBB1 (mRNA); ERBB (mRNA); EGFR (mRNA)
Gene Name EGFR
DTT Type
Clinical trial target
 [1]
BioChemical Class
mRNA target
UniProt ID
EGFR_HUMAN
TTD ID
T41560
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.10.1
Sequence
MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEV
VLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALA
VLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF
QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGC
TGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYV
VTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK
NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAF
ENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKL
FGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN
LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVM
GENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVV
ALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS
GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGI
CLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA
RNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY
GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPK
FRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQ
QGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED
SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLN
TVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRV
APQSSEFIGA
Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Plays a role in enhancing learning and memory performance.
KEGG Pathway
EGFR tyrosine kinase inhibitor resistance (hsa01521 )
Endocrine resistance (hsa01522 )
MAPK signaling pathway (hsa04010 )
ErbB signaling pathway (hsa04012 )
Ras signaling pathway (hsa04014 )
Rap1 signaling pathway (hsa04015 )
Calcium signaling pathway (hsa04020 )
HIF-1 signaling pathway (hsa04066 )
FoxO signaling pathway (hsa04068 )
Phospholipase D signaling pathway (hsa04072 )
Endocytosis (hsa04144 )
PI3K-Akt signaling pathway (hsa04151 )
Focal adhesion (hsa04510 )
Adherens junction (hsa04520 )
Gap junction (hsa04540 )
JAK-STAT signaling pathway (hsa04630 )
Regulation of actin cytoskeleton (hsa04810 )
GnRH signaling pathway (hsa04912 )
Estrogen signaling pathway (hsa04915 )
Oxytocin signaling pathway (hsa04921 )
Relaxin signaling pathway (hsa04926 )
Parathyroid hormone synthesis, secretion and action (hsa04928 )
Cushing syndrome (hsa04934 )
Epithelial cell signaling in Helicobacter pylori infection (hsa05120 )
Shigellosis (hsa05131 )
Hepatitis C (hsa05160 )
Human cytomegalovirus infection (hsa05163 )
Human papillomavirus infection (hsa05165 )
Coronavirus disease - COVID-19 (hsa05171 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
MicroRNAs in cancer (hsa05206 )
Chemical carcinogenesis - receptor activation (hsa05207 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Colorectal cancer (hsa05210 )
Pancreatic cancer (hsa05212 )
Endometrial cancer (hsa05213 )
Glioma (hsa05214 )
Prostate cancer (hsa05215 )
Melanoma (hsa05218 )
Bladder cancer (hsa05219 )
Non-small cell lung cancer (hsa05223 )
Breast cancer (hsa05224 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Central carbon metabolism in cancer (hsa05230 )
Choline metabolism in cancer (hsa05231 )
PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235 )
Reactome Pathway
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382 )
Signaling by ERBB4 (R-HSA-1236394 )
SHC1 events in ERBB2 signaling (R-HSA-1250196 )
PLCG1 events in ERBB2 signaling (R-HSA-1251932 )
PIP3 activates AKT signaling (R-HSA-1257604 )
Signaling by EGFR (R-HSA-177929 )
GRB2 events in EGFR signaling (R-HSA-179812 )
GAB1 signalosome (R-HSA-180292 )
SHC1 events in EGFR signaling (R-HSA-180336 )
EGFR downregulation (R-HSA-182971 )
GRB2 events in ERBB2 signaling (R-HSA-1963640 )
PI3K events in ERBB2 signaling (R-HSA-1963642 )
EGFR interacts with phospholipase C-gamma (R-HSA-212718 )
EGFR Transactivation by Gastrin (R-HSA-2179392 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
Signal transduction by L1 (R-HSA-445144 )
Constitutive Signaling by EGFRvIII (R-HSA-5637810 )
Inhibition of Signaling by Overexpressed EGFR (R-HSA-5638303 )
RAF/MAP kinase cascade (R-HSA-5673001 )
ERBB2 Regulates Cell Motility (R-HSA-6785631 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
ERBB2 Activates PTK6 Signaling (R-HSA-8847993 )
Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825 )
Clathrin-mediated endocytosis (R-HSA-8856828 )
PTK6 promotes HIF1A stabilization (R-HSA-8857538 )
Downregulation of ERBB2 signaling (R-HSA-8863795 )
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors (R-HSA-8866910 )
Extra-nuclear estrogen signaling (R-HSA-9009391 )
NOTCH3 Activation and Transmission of Signal to the Nucleus (R-HSA-9013507 )
HCMV Early Events (R-HSA-9609690 )
Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638 )
Signaling by ERBB2 KD Mutants (R-HSA-9664565 )
Signaling by ERBB2 ECD mutants (R-HSA-9665348 )
Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686 )
Signaling by ERBB2 (R-HSA-1227986 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
4 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AC0010 DMQRL2Y Non-small-cell lung cancer 2C25.Y Phase 3 [2]
CK-101 DMMVWSY Non-small-cell lung cancer 2C25.Y Phase 1/2 [2]
EGFR antisense DNA DMF7EX8 Head and neck cancer 2D42 Phase 1/2 [1]
Pyrotinib DMW7K39 Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Head and neck cancer 2C82 Head and neck tissue 5.84E-05 0.32 0.55
Psoriasis EA90 Skin 1.86E-07 -0.27 -0.42
Lung cancer 2C82 Lung tissue 1.65E-01 -0.04 -0.09
Breast cancer 2C82 Breast tissue 1.04E-65 -0.89 -1.53
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References

1 Antitumor Effects of EGFR Antisense Guanidine-Based Peptide Nucleic Acids in Cancer Models. ACS Chem Biol. 2013 February 15; 8(2): 345-352.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)