Protein:EGFR |
Protein Summary |
 Gene summary |
| Gene name: EGFR | ASpdb.0 ID: 1956 | Gene | Gene symbol | EGFR | Gene ID | 1956 |
| Gene name | epidermal growth factor receptor |
| Synonyms | ERBB|ERBB1|ERRP|HER1|NISBD2|PIG61|mENA |
| Cytomap | 7p11.2 |
| Type of gene | protein-coding |
| Description | epidermal growth factor receptorEGFR vIIIavian erythroblastic leukemia viral (v-erb-b) oncogene homologcell growth inhibiting protein 40cell proliferation-inducing protein 61epidermal growth factor receptor tyrosine kinase domainerb-b2 receptor tyro |
| Modification date | 20240416 |
| UniProtAcc | P00533 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | EGFR | GO:0001934 | positive regulation of protein phosphorylation | 20551055 |
| Gene | EGFR | GO:0003682 | chromatin binding | 20551055 |
| Gene | EGFR | GO:0004713 | protein tyrosine kinase activity | 2472218|9890893|17115032|17599051 |
| Gene | EGFR | GO:0004888 | transmembrane signaling receptor activity | 7736574 |
| Gene | EGFR | GO:0005006 | epidermal growth factor receptor activity | 12828935 |
| Gene | EGFR | GO:0005006 | epidermal growth factor receptor activity | 2176151|11336639|12435727|17115032 |
| Gene | EGFR | GO:0005634 | nucleus | 12828935|17115032|20551055 |
| Gene | EGFR | GO:0005737 | cytoplasm | 7588596|12435727|22298428 |
| Gene | EGFR | GO:0005768 | endosome | 16554368 |
| Gene | EGFR | GO:0005768 | endosome | 14702346|17182860|22732145 |
| Gene | EGFR | GO:0005886 | plasma membrane | 11331309|11336639|15611079 |
| Gene | EGFR | GO:0005886 | plasma membrane | 15465819|20462955|22298428|22732145 |
| Gene | EGFR | GO:0007165 | signal transduction | 10572067 |
| Gene | EGFR | GO:0007166 | cell surface receptor signaling pathway | 7736574 |
| Gene | EGFR | GO:0007173 | epidermal growth factor receptor signaling pathway | 7736574 |
| Gene | EGFR | GO:0007173 | epidermal growth factor receptor signaling pathway | 9890893|12435727|12828935 |
| Gene | EGFR | GO:0008284 | positive regulation of cell population proliferation | 7736574 |
| Gene | EGFR | GO:0009986 | cell surface | 25666625 |
| Gene | EGFR | GO:0010008 | endosome membrane | 22719997 |
| Gene | EGFR | GO:0016020 | membrane | 12435727 |
| Gene | EGFR | GO:0016323 | basolateral plasma membrane | 12646923 |
| Gene | EGFR | GO:0018108 | peptidyl-tyrosine phosphorylation | 22732145 |
| Gene | EGFR | GO:0030054 | cell junction | - |
| Gene | EGFR | GO:0030296 | protein tyrosine kinase activator activity | 2176151|11336639 |
| Gene | EGFR | GO:0030307 | positive regulation of cell growth | 15467833 |
| Gene | EGFR | GO:0031901 | early endosome membrane | 17714434 |
| Gene | EGFR | GO:0032587 | ruffle membrane | 11331309 |
| Gene | EGFR | GO:0032991 | protein-containing complex | 20878056 |
| Gene | EGFR | GO:0038134 | ERBB2-EGFR signaling pathway | 11336639 |
| Gene | EGFR | GO:0042177 | negative regulation of protein catabolic process | 17115032 |
| Gene | EGFR | GO:0042327 | positive regulation of phosphorylation | 15082764 |
| Gene | EGFR | GO:0043235 | receptor complex | 23382219 |
| Gene | EGFR | GO:0043406 | positive regulation of MAP kinase activity | 10572067 |
| Gene | EGFR | GO:0045121 | membrane raft | 12009895 |
| Gene | EGFR | GO:0045739 | positive regulation of DNA repair | 17115032 |
| Gene | EGFR | GO:0045740 | positive regulation of DNA replication | 17115032 |
| Gene | EGFR | GO:0045944 | positive regulation of transcription by RNA polymerase II | 20551055 |
| Gene | EGFR | GO:0050679 | positive regulation of epithelial cell proliferation | 10572067 |
| Gene | EGFR | GO:0051015 | actin filament binding | 14702346 |
| Gene | EGFR | GO:0070141 | response to UV-A | 18483258 |
| Gene | EGFR | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 20551055 |
| Gene | EGFR | GO:0071392 | cellular response to estradiol stimulus | 20551055 |
| Gene | EGFR | GO:0097489 | multivesicular body, internal vesicle lumen | 17714434 |
| Gene | EGFR | GO:0097708 | intracellular vesicle | 11331309 |
| Gene | EGFR | GO:1900020 | positive regulation of protein kinase C activity | 22732145 |
| Gene | EGFR | GO:1903078 | positive regulation of protein localization to plasma membrane | 22732145 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P00533-1 | P00533-1_3njp_A.pdb | 3NJP | X-ray | 3.3 | A | 25 | 638 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P00533 | EGFR | P00533-1 | P00533-2 | 1210 | 405 | 404 | 405 | Substitution | FL | LS | 404 | 405 |
| P00533 | EGFR | P00533-1 | P00533-2 | 1210 | 405 | 406 | 1210 | Deletion | none | none | 405 | 405 |
| P00533 | EGFR | P00533-1 | P00533-3 | 1210 | 705 | 628 | 705 | Substitution | CTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLR | PGNESLKAMLFCLFKLSSCNQSNDGSVSHQSGSPAAQESCLGWIPSLLPSEFQLGWGGCSHLHAWPSASVIITASSCH | 628 | 705 |
| P00533 | EGFR | P00533-1 | P00533-3 | 1210 | 705 | 706 | 1210 | Deletion | none | none | 705 | 705 |
| P00533 | EGFR | P00533-1 | P00533-4 | 1210 | 628 | 628 | 628 | Substitution | C | S | 628 | 628 |
| P00533 | EGFR | P00533-1 | P00533-4 | 1210 | 628 | 629 | 1210 | Deletion | none | none | 628 | 628 |
| Multiple sequence alignment of our canonical and alternatively spliced EGFR |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of EGFR |
| UniProt-id | ENSG | ENST | ENSP |
| P00533-1 | ENSG00000146648.21 | ENST00000275493.7 | ENSP00000275493.2 |
| P00533-2 | ENSG00000146648.21 | ENST00000420316.6 | ENSP00000413843.2 |
| P00533-3 | ENSG00000146648.21 | ENST00000344576.7 | ENSP00000345973.2 |
| P00533-4 | ENSG00000146648.21 | ENST00000342916.7 | ENSP00000342376.3 |
| UniProt-id | NM ID | NP ID |
| P00533-1 | NM_005228.4 | NP_005219.2 |
| P00533-2 | NM_201283.1 | NP_958440.1 |
| P00533-3 | NM_201284.1 | NP_958441.1 |
| P00533-4 | NM_201282.1 | NP_958439.1 |
| Amino acid sequences of our canonical and alternatively spliced EGFR |
| accession_id | Protein sequence |
| P00533-1 | MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVL IALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLY NPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGL RSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGCTG PGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIG SQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLP SPTDSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLNTVQPTCVNSTFDSPAHWAQKGSHQISLDNP |
| P00533-2 | MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVL IALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLY NPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK |
| P00533-3 | MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVL IALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLY NPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGL RSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGPGN |
| P00533-4 | MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVL IALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLY NPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGL RSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| EGFR (go to UniProt):P00533 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P00533 | Topological domain | 25 | 645 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=404;End=405 |
| P00533 | Topological domain | 25 | 645 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=406;End=1210 |
| P00533 | Topological domain | 25 | 645 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=628;End=705 |
| P00533 | Topological domain | 25 | 645 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=628;End=628 |
| P00533 | Topological domain | 25 | 645 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=629;End=1210 |
| P00533 | Transmembrane | 646 | 668 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=406;End=1210 |
| P00533 | Transmembrane | 646 | 668 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=628;End=705 |
| P00533 | Transmembrane | 646 | 668 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=629;End=1210 |
| P00533 | Topological domain | 669 | 1210 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=406;End=1210 |
| P00533 | Topological domain | 669 | 1210 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=628;End=705 |
| P00533 | Topological domain | 669 | 1210 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=706;End=1210 |
| P00533 | Topological domain | 669 | 1210 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=629;End=1210 |
| P00533 | Repeat | 390 | 600 | Note=Approximate | Type=Substitution;Start=404;End=405 |
| P00533 | Repeat | 390 | 600 | Note=Approximate | Type=Deletion;Start=406;End=1210 |
| P00533 | Domain | 712 | 979 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=406;End=1210 |
| P00533 | Domain | 712 | 979 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=706;End=1210 |
| P00533 | Domain | 712 | 979 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=629;End=1210 |
| P00533 | Region | 688 | 704 | Note=Important for dimerization%2C phosphorylation and activation | Type=Deletion;Start=406;End=1210 |
| P00533 | Region | 688 | 704 | Note=Important for dimerization%2C phosphorylation and activation | Type=Substitution;Start=628;End=705 |
| P00533 | Region | 688 | 704 | Note=Important for dimerization%2C phosphorylation and activation | Type=Deletion;Start=629;End=1210 |
| P00533 | Region | 1097 | 1137 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=406;End=1210 |
| P00533 | Region | 1097 | 1137 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=706;End=1210 |
| P00533 | Region | 1097 | 1137 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=629;End=1210 |
| P00533 | Compositional bias | 1099 | 1114 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=406;End=1210 |
| P00533 | Compositional bias | 1099 | 1114 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=706;End=1210 |
| P00533 | Compositional bias | 1099 | 1114 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=629;End=1210 |
Gene Isoform Structures and Expression Levels for EGFR |
| Gene structures of our canonical and alternative spliced genes of EGFR * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P00533-1 |
| 3D view using mol* of P00533-2 |
| 3D view using mol* of P00533-3 |
| 3D view using mol* of P00533-4 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P00533-1 |
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| pLDDT distribution across the protein length of P00533-2 |
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| pLDDT distribution across the protein length of P00533-3 |
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| pLDDT distribution across the protein length of P00533-4 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P00533-1 |
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| Ramachandran plot of P00533-2 |
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| Ramachandran plot of P00533-3 |
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| Ramachandran plot of P00533-4 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P00533-1 | 1.06 | 368 | 1.067 | 867.104 | 0.424 | 0.788 | 1.011 | 0.671 | 1.061 | 0.632 | 1.137 | 719,720,721,722,723,724,726,743,745,747,748,749,75 9,762,766,777,788,790,797,799,800,803,836,837,841, 842,844,854,855,857,858,874,875,876,877,878,879,88 0,891,906,913,914,919,920,1067,1068,1069,1070,1071 ,1072,1073,1074,1076,1077 |
| P00533-2 | 1.009 | 186 | 0.987 | 600.593 | 0.637 | 0.712 | 0.892 | 0.279 | 1.164 | 0.24 | 0.811 | 25,27,28,30,32,60,62,63,84,86,105,108,110,142,144, 145,167,168,169,170,172,212,220,221,222,232,233,23 4,236,237,246,248,249,250,251,252,253,254,255,258, 260,286,287,288,289,290,292,299,306,307,308,309,31 0 |
| P00533-3 | 1.01 | 268 | 0.99 | 737.107 | 0.591 | 0.713 | 0.882 | 0.265 | 1.158 | 0.229 | 0.678 | 25,27,28,30,32,60,62,63,83,84,86,105,108,110,111,1 42,144,145,167,168,169,170,212,220,221,222,232,233 ,234,236,237,246,248,249,250,251,252,253,254,255,2 57,258,260,286,287,288,289,290,291,292,293,294,299 ,306,307,308,309,310 |
| P00533-4 | 1.137 | 163 | 0.977 | 318.304 | 0.356 | 0.903 | 1.256 | 0.176 | 1.549 | 0.114 | 0.631 | 32,33,34,35,36,37,38,39,41,47,50,51,54,63,64,66,68 ,69,111,309,340,341,342,343,346,347,348,349,366,36 7,368,370,372,402,404,406,430,431,432,433,434 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P00533-1_P00533-1_3njp_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P00533-1_3njp_A_P00533-2.pdb |
| 3D view using mol* of P00533-1_3njp_A_P00533-3.pdb |
| 3D view using mol* of P00533-1_3njp_A_P00533-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P00533-1_P00533-2.pdb |
| 3D view using mol* of P00533-1_P00533-3.pdb |
| 3D view using mol* of P00533-1_P00533-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P00533-1_vs_P00533-2.png |
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| ./stats/secondary_structure/figure/P00533-1_vs_P00533-3.png |
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| ./stats/secondary_structure/figure/P00533-1_vs_P00533-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P00533-1_vs_P00533-2.png |
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| ./stats/relative_asa/P00533-1_vs_P00533-3.png |
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| ./stats/relative_asa/P00533-1_vs_P00533-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to EGFR |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P00533 | EGFR | DB16695 | Amivantamab | approved, investigational | antibody, downregulator |
| P00533 | EGFR | DB01269 | Panitumumab | approved, investigational | suppressor |
| P00533 | EGFR | DB13164 | Olmutinib | investigational | inhibitor |
| P00533 | EGFR | DB05524 | Pelitinib | investigational | |
| P00533 | EGFR | DB01259 | Lapatinib | approved, investigational | antagonist |
| P00533 | EGFR | DB07662 | PD-168393 | experimental | |
| P00533 | EGFR | DB07602 | S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE | experimental | |
| P00533 | EGFR | DB05944 | Varlitinib | investigational | |
| P00533 | EGFR | DB15035 | Zanubrutinib | approved, investigational | inhibitor |
| P00533 | EGFR | DB05424 | Canertinib | investigational | |
| P00533 | EGFR | DB15327 | Abivertinib | investigational | inhibitor |
| P00533 | EGFR | DB06021 | AV-412 | investigational | |
| P00533 | EGFR | DB00281 | Lidocaine | approved, vet_approved | antagonist |
| P00533 | EGFR | DB16390 | Mobocertinib | approved, investigational | inhibitor |
| P00533 | EGFR | DB00317 | Gefitinib | approved, investigational | antagonist |
| P00533 | EGFR | DB10772 | Foreskin keratinocyte (neonatal) | approved | agonist |
| P00533 | EGFR | DB05294 | Vandetanib | approved | inhibitor |
| P00533 | EGFR | DB03496 | Alvocidib | experimental, investigational | |
| P00533 | EGFR | DB09559 | Necitumumab | approved, investigational | antagonist |
| P00533 | EGFR | DB09330 | Osimertinib | approved | inhibitor, regulator |
| P00533 | EGFR | DB11731 | Depatuxizumab mafodotin | investigational | antibody |
| P00533 | EGFR | DB11737 | Icotinib | experimental, investigational | antagonist |
| P00533 | EGFR | DB11828 | Neratinib | approved, investigational | inhibitor |
| P00533 | EGFR | DB11963 | Dacomitinib | approved, investigational | inhibitor |
| P00533 | EGFR | DB05374 | Rindopepimut | investigational | |
| P00533 | EGFR | DB00002 | Cetuximab | approved | binder |
| P00533 | EGFR | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P00533 | EGFR | DB08916 | Afatinib | approved | inhibitor |
| P00533 | EGFR | DB04988 | IGN311 | investigational | |
| P00533 | EGFR | DB05101 | Matuzumab | investigational | |
| P00533 | EGFR | DB12114 | Poziotinib | investigational | inhibitor, binder |
| P00533 | EGFR | DB12202 | Zalutumumab | investigational | antagonist |
| P00533 | EGFR | DB12267 | Brigatinib | approved, investigational | inhibitor |
| P00533 | EGFR | DB00530 | Erlotinib | approved, investigational | antagonist |
Related Diseases to EGFR |
| Previous studies relating to the alternative splicing of EGFR and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| EGFR | 7588596 | WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. | The Wilms tumor suppressor gene WT1 encodes a developmentally regulated transcription factor that is mutated in a subset of embryonal tumors. To test its functional properties, we developed osteosarcoma cell lines expressing WT1 under an inducible tetracycline-regulated promoter. Induction of WT1 resulted in programmed cell death. This effect, which was differentially mediated by the alternative splicing variants of WT1, was independent of p53. WT1-mediated apoptosis was associated with reduced synthesis of the epidermal growth factor receptor (EGFR), but not of other postulated WT1-target genes, and it was abrogated by constitutive expression of EGFR. WT1 repressed transcription from the EGFR promoter, binding to two TC-rich repeat sequences. In the developing kidney, EGFR expression in renal precursor cells declined with the onset of WT1 expression. Repression of EGFR and induction of apoptosis by mechanism that may contribute to its critical role in normal kidney development and to the immortalization of tumor cells with inactivated WT1 alleles. | D012516 | Osteosarcoma |
| EGFR | 16596194 | Differential expression of alternatively spliced mRNA forms of the insulin-like growth factor 1 receptor in human neuroendocrine tumors. | The activation of the insulin-like growth factor 1/IGF1 receptor system (IGF1/IGF1R) is a critical event in the transformation and tumorigenicity processes in a wide variety of human tumors. The IGF1/IGF1R system has been recently studied in carcinoid tumors that often arise in the gastrointestinal tract; these tumors are characterized by hypersecretion of bioamines and neuropeptides, leading to functional tumor disease. Two alternatively spliced IGF1R mRNA transcripts have been described to differ by only three nucleotides (CAG) in the coding sequence, resulting in an amino-acid change from the originally described Thr-Gly to an Arg in the extracellular portion of the receptor beta subunit. In transfected Chinese hamster ovary cells, the form without CAG (CAG-) exhibited an approximate 2-fold increase in IGF1 stimulation of activities required for its mitogenic properties. In this study, we examine the relative expression of the two IGF1R mRNA isoforms by a semiquantitative RT-PCR approach using highly standardized conditions, beta-2 microglobulin (B2M) as a reference gene and gel imaging analysis. We analyzed a large series of human neuroendocrine tumors (32 samples) and 9 normal tissues. A significant higher expression of both isoforms in the tumor samples (approximately 2-fold increase) was found, while a constant CAG+/CAG- IGF1R mRNA isoforms of an approximate 3:1 ratio was observed in all tumoral and normal cell types studied. The phylogenetic study of the IGF1R locus in several species suggests that human IGF1R CAG- mRNA isoform is evolutionarily more recent compared to the IGF1R CAG+ mRNA isoform and it could be used by the splicing apparatus at this intron/exon junction with a lower efficiency. This study highlights the relevance of IGF1R mRNA expression in neuroendocrine tumor cells, and the constant presence of 'subtle' alternative splicing for the IGF1R locus. | D018273 | Carcinoma, Islet Cell |
| EGFR | 16596194 | Differential expression of alternatively spliced mRNA forms of the insulin-like growth factor 1 receptor in human neuroendocrine tumors. | The activation of the insulin-like growth factor 1/IGF1 receptor system (IGF1/IGF1R) is a critical event in the transformation and tumorigenicity processes in a wide variety of human tumors. The IGF1/IGF1R system has been recently studied in carcinoid tumors that often arise in the gastrointestinal tract; these tumors are characterized by hypersecretion of bioamines and neuropeptides, leading to functional tumor disease. Two alternatively spliced IGF1R mRNA transcripts have been described to differ by only three nucleotides (CAG) in the coding sequence, resulting in an amino-acid change from the originally described Thr-Gly to an Arg in the extracellular portion of the receptor beta subunit. In transfected Chinese hamster ovary cells, the form without CAG (CAG-) exhibited an approximate 2-fold increase in IGF1 stimulation of activities required for its mitogenic properties. In this study, we examine the relative expression of the two IGF1R mRNA isoforms by a semiquantitative RT-PCR approach using highly standardized conditions, beta-2 microglobulin (B2M) as a reference gene and gel imaging analysis. We analyzed a large series of human neuroendocrine tumors (32 samples) and 9 normal tissues. A significant higher expression of both isoforms in the tumor samples (approximately 2-fold increase) was found, while a constant CAG+/CAG- IGF1R mRNA isoforms of an approximate 3:1 ratio was observed in all tumoral and normal cell types studied. The phylogenetic study of the IGF1R locus in several species suggests that human IGF1R CAG- mRNA isoform is evolutionarily more recent compared to the IGF1R CAG+ mRNA isoform and it could be used by the splicing apparatus at this intron/exon junction with a lower efficiency. This study highlights the relevance of IGF1R mRNA expression in neuroendocrine tumor cells, and the constant presence of 'subtle' alternative splicing for the IGF1R locus. | D006258 | Head and Neck Neoplasms |
| EGFR | 16596194 | Differential expression of alternatively spliced mRNA forms of the insulin-like growth factor 1 receptor in human neuroendocrine tumors. | The activation of the insulin-like growth factor 1/IGF1 receptor system (IGF1/IGF1R) is a critical event in the transformation and tumorigenicity processes in a wide variety of human tumors. The IGF1/IGF1R system has been recently studied in carcinoid tumors that often arise in the gastrointestinal tract; these tumors are characterized by hypersecretion of bioamines and neuropeptides, leading to functional tumor disease. Two alternatively spliced IGF1R mRNA transcripts have been described to differ by only three nucleotides (CAG) in the coding sequence, resulting in an amino-acid change from the originally described Thr-Gly to an Arg in the extracellular portion of the receptor beta subunit. In transfected Chinese hamster ovary cells, the form without CAG (CAG-) exhibited an approximate 2-fold increase in IGF1 stimulation of activities required for its mitogenic properties. In this study, we examine the relative expression of the two IGF1R mRNA isoforms by a semiquantitative RT-PCR approach using highly standardized conditions, beta-2 microglobulin (B2M) as a reference gene and gel imaging analysis. We analyzed a large series of human neuroendocrine tumors (32 samples) and 9 normal tissues. A significant higher expression of both isoforms in the tumor samples (approximately 2-fold increase) was found, while a constant CAG+/CAG- IGF1R mRNA isoforms of an approximate 3:1 ratio was observed in all tumoral and normal cell types studied. The phylogenetic study of the IGF1R locus in several species suggests that human IGF1R CAG- mRNA isoform is evolutionarily more recent compared to the IGF1R CAG+ mRNA isoform and it could be used by the splicing apparatus at this intron/exon junction with a lower efficiency. This study highlights the relevance of IGF1R mRNA expression in neuroendocrine tumor cells, and the constant presence of 'subtle' alternative splicing for the IGF1R locus. | D018358 | Neuroendocrine Tumors |
| EGFR | 22537942 | Differential expression of RBM5, EGFR and KRAS mRNA and protein in non-small cell lung cancer tissues. | RNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes. This study aimed to detect RBM5 expression in non-small cell lung cancer (NSCLC) and to associate RBM5 expression with clinicopathological data from NSCLC patients and EGFR and KRAS expression to better understand the potential role of RBM5 in NSCLC. | D002289 | Carcinoma, Non-Small-Cell Lung |
| EGFR | 22537942 | Differential expression of RBM5, EGFR and KRAS mRNA and protein in non-small cell lung cancer tissues. | RNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes. This study aimed to detect RBM5 expression in non-small cell lung cancer (NSCLC) and to associate RBM5 expression with clinicopathological data from NSCLC patients and EGFR and KRAS expression to better understand the potential role of RBM5 in NSCLC. | D008175 | Lung Neoplasms |
| EGFR | 22623992 | EGFR soluble isoforms and their transcripts are expressed in meningiomas. | The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of many tumors. In addition to the full-length EGFR (isoform a), normal and tumor cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain. sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2), 3 (v3) and 4 (v4) mRNA resulting from gene alternative splicing. Accordingly, the results of EGFR protein expression analysis depend on the domain targeted by the antibodies. In meningiomas, EGFR expression investigations mainly focused on EGFR isoform a. sEGFR and EGFRvIII mutant, that encodes a constitutively active truncated receptor, have not been studied. In a 69 meningiomas series, protein expression was analyzed by immunohistochemistry using extracellular domain targeted antibody (ECD-Ab) and intracellular domain targeted antibody (ICD-Ab). EGFRv1 to v4 and EGFRvIII mRNAs were quantified by RT-PCR and EGFR amplification revealed by MLPA. Results were analyzed with respect to clinical data, tumor resection (Simpson grade), histological type, tumor grade, and patient outcome.Immunochemical staining was stronger with ECD-Ab than with ICD-Ab. Meningiomas expressed EGFRv1 to -v4 mRNAs but not EGFRvIII mutant. Intermediate or high ECD-Ab staining and high EGFRv1 to v4 mRNA levels were associated to a better progression free survival (PFS). PFS was also improved in women, when tumor resection was evaluated as Simpson 1 or 2, in grade I vs. grade II and III meningiomas and when Ki67 labeling index was lower than 10%. Our results suggest that, EGFR protein isoforms without ICD and their corresponding mRNA variants are expressed in meningiomas in addition to the whole isoform a. EGFRvIII was not expressed. High expression levels seem to be related to a better prognosis. These results indicate that the oncogenetic mechanisms involving the EGFR pathway in meningiomas could be different from other tumor types. | D008579 | Meningioma |
| EGFR | 23633480 | Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors. | Insulin receptor (IR) exists as two isoforms resulting from the alternative splicing of IR pre-mRNA. IR-B promotes the metabolic effects of insulin, whereas IR-A rather signals proliferative effects. IR-B is predominantly expressed in the adult liver. Here, we show that the alternative splicing of IR pre-mRNA is dysregulated in a panel of 85 human hepatocellular carcinoma (HCC) while being normal in adjacent nontumor liver tissue. An IR-B to IR-A switch is frequently observed in HCC tumors regardless of tumor etiology. Using pharmacologic and siRNA approaches, we show that the autocrine or paracrine activation of the EGF receptor (EGFR)/mitogen-activated protein/extracellular signal-regulated kinase pathway increases the IR-A:IR-B ratio in HCC cell lines, but not in normal hepatocytes, by upregulating the expression of the splicing factors CUGBP1, hnRNPH, hnRNPA1, hnRNPA2B1, and SF2/ASF. In HCC tumors, there is a significant correlation between the expression of IR-A and that of splicing factors. Dysregulation of IR pre-mRNA splicing was confirmed in a chemically induced model of HCC in rat but not in regenerating livers after partial hepatectomy. This study identifies a mechanism responsible for the generation of mitogenic IR-A and provides a novel interplay between IR and EGFR pathways in HCC. Increased expression of IR-A during neoplastic transformation of hepatocytes could mediate some of the adverse effects of hyperinsulinemia on HCC. | D006528 | Carcinoma, Hepatocellular |
| EGFR | 23633480 | Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors. | Insulin receptor (IR) exists as two isoforms resulting from the alternative splicing of IR pre-mRNA. IR-B promotes the metabolic effects of insulin, whereas IR-A rather signals proliferative effects. IR-B is predominantly expressed in the adult liver. Here, we show that the alternative splicing of IR pre-mRNA is dysregulated in a panel of 85 human hepatocellular carcinoma (HCC) while being normal in adjacent nontumor liver tissue. An IR-B to IR-A switch is frequently observed in HCC tumors regardless of tumor etiology. Using pharmacologic and siRNA approaches, we show that the autocrine or paracrine activation of the EGF receptor (EGFR)/mitogen-activated protein/extracellular signal-regulated kinase pathway increases the IR-A:IR-B ratio in HCC cell lines, but not in normal hepatocytes, by upregulating the expression of the splicing factors CUGBP1, hnRNPH, hnRNPA1, hnRNPA2B1, and SF2/ASF. In HCC tumors, there is a significant correlation between the expression of IR-A and that of splicing factors. Dysregulation of IR pre-mRNA splicing was confirmed in a chemically induced model of HCC in rat but not in regenerating livers after partial hepatectomy. This study identifies a mechanism responsible for the generation of mitogenic IR-A and provides a novel interplay between IR and EGFR pathways in HCC. Increased expression of IR-A during neoplastic transformation of hepatocytes could mediate some of the adverse effects of hyperinsulinemia on HCC. | D002471 | Cell Transformation, Neoplastic |
| EGFR | 23633480 | Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors. | Insulin receptor (IR) exists as two isoforms resulting from the alternative splicing of IR pre-mRNA. IR-B promotes the metabolic effects of insulin, whereas IR-A rather signals proliferative effects. IR-B is predominantly expressed in the adult liver. Here, we show that the alternative splicing of IR pre-mRNA is dysregulated in a panel of 85 human hepatocellular carcinoma (HCC) while being normal in adjacent nontumor liver tissue. An IR-B to IR-A switch is frequently observed in HCC tumors regardless of tumor etiology. Using pharmacologic and siRNA approaches, we show that the autocrine or paracrine activation of the EGF receptor (EGFR)/mitogen-activated protein/extracellular signal-regulated kinase pathway increases the IR-A:IR-B ratio in HCC cell lines, but not in normal hepatocytes, by upregulating the expression of the splicing factors CUGBP1, hnRNPH, hnRNPA1, hnRNPA2B1, and SF2/ASF. In HCC tumors, there is a significant correlation between the expression of IR-A and that of splicing factors. Dysregulation of IR pre-mRNA splicing was confirmed in a chemically induced model of HCC in rat but not in regenerating livers after partial hepatectomy. This study identifies a mechanism responsible for the generation of mitogenic IR-A and provides a novel interplay between IR and EGFR pathways in HCC. Increased expression of IR-A during neoplastic transformation of hepatocytes could mediate some of the adverse effects of hyperinsulinemia on HCC. | D008114 | Liver Neoplasms, Experimental |
| EGFR | 23707073 | EGFR mutation-induced alternative splicing of Max contributes to growth of glycolytic tumors in brain cancer. | Alternative splicing contributes to diverse aspects of cancer pathogenesis including altered cellular metabolism, but the specificity of the process or its consequences are not well understood. We characterized genome-wide alternative splicing induced by the activating EGFRvIII mutation in glioblastoma (GBM). EGFRvIII upregulates the heterogeneous nuclear ribonucleoprotein (hnRNP) A1 splicing factor, promoting glycolytic gene expression and conferring significantly shorter survival in patients. HnRNPA1 promotes splicing of a transcript encoding the Myc-interacting partner Max, generating Delta Max, an enhancer of Myc-dependent transformation. Delta Max, but not full-length Max, rescues Myc-dependent glycolytic gene expression upon induced EGFRvIII loss, and correlates with hnRNPA1 expression and downstream Myc-dependent gene transcription in patients. Finally, Delta Max is shown to promote glioma cell proliferation in vitro and augment EGFRvIII expressing GBM growth in vivo. These results demonstrate an important role for alternative splicing in GBM and identify Delta Max as a mediator of Myc-dependent tumor cell metabolism. | D005909 | Glioblastoma |
| EGFR | 24802673 | A new class of protein cancer biomarker candidates: differentially expressed splice variants of ERBB2 (HER2/neu) and ERBB1 (EGFR) in breast cancer cell lines. | Combined RNA-Seq and proteomics analyses reveal striking differential expression of splice isoforms of key proteins in important cancer pathways and networks. Even between primary tumor cell lines from histologically similar inflammatory breast cancers, we find striking differences in hormone receptor-negative cell lines that are ERBB2 (Her2/neu)-amplified versus ERBB1 (EGFR) over-expressed with low ERBB2 activity. We have related these findings to protein-protein interaction networks, signaling and metabolic pathways, and methods for predicting functional variants among multiple alternative isoforms. Understanding the upstream ligands and regulators and the downstream pathways and interaction networks for ERBB receptors is certain to be important for explanation and prediction of the variable levels of expression and therapeutic responses of ERBB+tumors in the breast and in other organ sites. Alternative splicing is a remarkable evolutionary development that increases protein diversity from multi-exonic genes without requiring expansion of the genome. It is no longer sufficient to report the up- or down-expression of genes and proteins without dissecting the complexity due to alternative splicing. This article is part of a Special Issue entitled: 20Years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini , Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez. | D001943 | Breast Neoplasms |
| EGFR | 36403890 | Implicative role of epidermal growth factor receptor and its associated signaling partners in the pathogenesis of Alzheimer's disease. | Epidermal growth factor receptor (EGFR) plays a pivotal role in early brain development, although its expression pattern declines in accordance with the maturation of the active nervous system. However, recurrence of EGFR expression in brain cells takes place during neural functioning decline and brain atrophy in order to maintain the homeostatic neuronal pool. As a consequence, neurotoxic lesions such as amyloid beta fragment (Aβ1-42) formed during the alternative splicing of amyloid precursor protein in Alzheimer's disease (AD) elevate the expression of EGFR. This inappropriate peptide deposition on EGFR results in the sustained phosphorylation of the downstream signaling axis, leading to extensive Aβ1-42 production and tau phosphorylation as subsequent pathogenesis. Recent reports convey that the pathophysiology of AD is correlated with EGFR and its associated membrane receptor complex molecules. One such family of molecules is the annexin superfamily, which has synergistic relationships with EGFR and is known for membrane-bound signaling that contributes to a variety of inflammatory responses. Besides, Galectin-3, tissue-type activated plasminogen activator, and many more, which lineate the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18) result in severe neuronal loss. Altogether, we emphasized the perspectives of cellular senescence up-regulated by EGFR and its associated membrane receptor molecules in the pathogenesis of AD as a target for a therapeutical alternative to intervene in AD. | D000544 | Alzheimer Disease |
Clinically important variants in EGFR |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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