Details of Host Protein

 Host Protein General Information (ID: PT0391)
  Protein Name
Epidermal growth factor receptor (EGFR)
  Gene Name
EGFR
  Host Species
Homo sapiens
  Uniprot Entry Name
EGFR_HUMAN
  Protein Families
Protein kinase superfamily
  EC Number
2.7.1..1
  Subcellular Location
Cell membrane
  External Link
NCBI Gene ID
1956
Uniprot ID
P00533
Ensembl ID
ENSG00000146648
HGNC ID
HGNC:3236
  Function in Host
Receptor tyrosine kinase binding ligands of the EGF familyand activating several signaling cascades to convert extracellular cuesinto 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 receptorhomo- and/or heterodimerization and autophosphorylation on keycytoplasmic residues. The phosphorylated receptor recruits adapterproteins like GRB2 which in turn activates complex downstream signalingcascades. Activates at least 4 major downstream signaling cascadesincluding the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATsmodules. May also activate the NF-kappa-B signalingcascade. Also directly phosphorylates other proteinslike RGS16, activating its GTPase activity and probably coupling theEGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases itsinteraction with SRC and CTNNB1/beta-catenin. Positively regulates cell migration via interaction with CCDC88A/GIVwhich retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration. Plays a role in enhancing learning and memoryperformance. [1-10]
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  Related KEGG Pathway
Coronavirus disease - COVID-19 hsa05171            Pathway Map 
Hepatitis C hsa05160            Pathway Map 
Human cytomegalovirus infection hsa05163            Pathway Map 
Human papillomavirus infection hsa05165            Pathway Map 
Epithelial cell signaling in Helicobacter pylori infection hsa05120            Pathway Map 
Shigellosis hsa05131            Pathway Map 
Non-small cell lung cancer hsa05223            Pathway Map 
MAPK signaling pathway hsa04010            Pathway Map 
  3D Structure
PDB ID: 1IVO 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [11]
Infected TissueLung Infection Time7-9 Days
Infected CellCalu-3 Cells (Human epithelial cell line) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein EGFR in viral infection, EGFR protein knockout Calu-3 Cells were infected with SARS-COV-2 for 7 - 9 Days , and the effects on infection was detected through CRISPR-based genome-wide gene-knockout screen.
ResultsIt is reported that knockout of EGFR increases SARS-CoV-2 RNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: Not Specified Virus Region (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [12]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7 cells (liver carcinoma cell)  (CVCL_0336 )
              Cell Originated Tissue Liver
              Infection Time 24h
              Interaction Score log2FC = 4.84472E+13
              Method Description RNA antisense purification and quantitative mass spectrometry (RAP-MS); Tandem mass tag (TMT) labelling; liquid chromatography tandem mass spectrometry (LC-MS/MS); Westernblot

Differential Gene Expression During SARS-COV-2 Infection
GEO Accession: GSE152641
Sample Type: Blood
Samples Details: Healthy Control: 24; COVID-19: 62
Platform: GPL24676 Illumina NovaSeq 6000
  PNG Download  
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GEO Accession: GSE162835
Sample Type: Nasopharyngeal Swabs
Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3
Platform: GPL24676 Illumina NovaSeq 6000
  PNG Download  
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GEO Accession: GSE175779
Sample Type: Human Bronchial Epithelial Cells
Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)
Platform: GPL18573 Illumina NextSeq 500
  PNG Download  
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Protein Phosphorylation after Virus Infection
S1064 [13]
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S1166 [13]
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S695 [13]
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S991 [13]
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S995 [13]
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T693 [13]
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T993 [13]
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Potential Drug(s) that Targets This Protein
Drug Name DrunkBank ID Pubchem ID TTD ID REF
Abivertinib DB15327  72734520  . [14]
Afatinib DB08916  10184653  D05UFG  [15]
Alvocidib DB03496  5287969  D0LF1U  [15]
AV-412 DB06021  9806229  . [15]
Brigatinib DB12267  68165256  D08PIE  [15]
Canertinib DB05424  156414  D0YB3W  [15]
Cetuximab DB00002  136170999  D0N5OV  [15]
Dacomitinib DB11963  11511120  D06XXH  [16]
Erlotinib DB00530  176870  D07POC  [15]
Foreskin keratinocyte (neonatal) DB10772  404770464  . [15]
Fostamatinib DB12010  11671467  D0V8HJ  [14]
Gefitinib DB00317  123631  D09XZB  [15]
Icotinib DB11737  22024915  D06WRJ  [15]
IGN311 DB04988  347909877  . [15]
Lapatinib DB01259  208908  D08CDI  [15]
Lidocaine DB00281  3676  D0X4RN  [15]
Lopinavir DB01601  92727  D0U5GB  [17]
Matuzumab DB05101  135314357  D0BZ7V  [15]
Necitumumab DB09559  135626739  D03WPP  [15]
Neratinib DB11828  9915743  D0Q9CY  [15]
Olmutinib DB13164  54758501  . [15]
Osimertinib DB09330  71496458  D0O8GK  [15]
Panitumumab DB01269  135300957  D0HU9H  [15]
PD-168393 DB07662  4708  D01VFR  [15]
Pelitinib DB05524  6445562  D0S3PO  [15]
PF299804 DB12013  11787114  D0V11HJ  [18]
Rindopepimut DB05374  135326939  D05FRP  [15]
Ritonavir DB00503  392622  D0ZU9R  [17]
S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE DB07602  46937083  . [15]
SGN-CD19A DB11731  86278355  . [15]
Triparanol . . . [17]
Triparanol . . . [15]
Vandetanib DB05294  3081361  D0G6QF  [15]
Varlitinib DB05944  42642648  D00NYJ  [15]
Vitamin C DB14482  54670067  D07AHW  [17]
Vitamin E DB00163  14985  D02TQO  [17]
Zalutumumab DB12202  135329978  D0R4PW  [15]
Zanubrutinib DB15035  135565884  D0UT4W  [15]

Protein Sequence Information
MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLNTVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRVAPQSSEFIGA
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References
1 The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B Identification of a novel receptor-tyrosine kinase signalosome. J Biol Chem. 2001 Mar 23;276(12):8865-74.
2 Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor and p185erbB2 Evidence that amphiregulin acts exclusively through the epidermal growth factor receptor at the surface of human epithelial cells. J Biol Chem. 1993 Feb 5;268(4):2924-31.
3 Recombinant human betacellulin Molecular structure, biological activities, and receptor interaction. J Biol Chem. 1994 Apr 1;269(13):9966-73.
4 Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling. Mol Cell. 2016 May 5;62(3):385-396.
5 Structural evidence for loose linkage between ligand binding and kinase activation in the epidermal growth factor receptor. Mol Cell Biol. 2010 Nov;30(22):5432-43.
6 The phosphoinositide kinase PIKfyve mediates epidermal growth factor receptor trafficking to the nucleus. Cancer Res. 2007 Oct 1;67(19):9229-37.
7 Epigen, the last ligand of ErbB receptors, reveals intricate relationships between affinity and mitogenicity. J Biol Chem. 2005 Mar 4;280(9):8503-12.
8 Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. Cell. 2002 Sep 20;110(6):763-73.
9 Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. Oncogene. 1997 Dec 4;15(23):2841-8.
10 Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation. Cell. 1989 Oct 6;59(1):33-43.
11 Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2. Nat Commun. 2022 Apr 25;13(1):2237.
12 The SARS-CoV-2 RNA-protein interactome in infected human cells. Nat Microbiol. 2021 Mar;6(3):339-353.
13 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
14 DrugBank
15 Interactomes of SARS-CoV-2 and human coronaviruses reveal host factors potentially affecting pathogenesis. EMBO J. 2021 Sep 1;40(17):e107776.
16 Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2. Cell Rep. 2021 Apr 6;35(1):108959.
17 Network analysis and molecular mapping for SARS-CoV-2 to reveal drug targets and repurposing of clinically developed drugs. Virology. 2021 Mar;555:10-18.
18 Attacking COVID-19 Progression Using Multi-Drug Therapy for Synergetic Target Engagement. Biomolecules. 2021 May 23;11(6):787.