Gene Name
EGFR
essential gene (from dbNSFP)
UniProt accession
P00533
Ensembl protein identifier
ENSP00000275493
Long Name
epidermal growth factor receptor
Summary
The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene.
Kinase Group
Tyr: tyrosine protein kinase. (Log odds ratio: 0.628591)
FDA approved inhibitors
Drug Sponsor Indications Target
Afatinib Boehringer Ingelheim Advanced non-small cell lung cancer EGFR, ErbB family (irreversible)
Erlotinib Roche Advanced non-small cell lung cancer and pancreatic cancer EGFR
Gefitinib AstraZeneca, Teva Advanced non-small cell lung cancer with EGFR mutation EGFR
Lapatinib GlaxoSmithKline HER2-positive advanced breast cancer HER2, ErbB2, EGFR
Panitumumab Amgen Colorectal cancer EGFR
Vandetanib AstraZeneca Advanced medullary thyroid cancer VEGFR, EGFR, RET, BRK, TIE2, SRC, EPHR

GO terms

Gene Ontology - Biological Process Log-odds ratio
GO:0048546 digestive tract morphogenesis 2.8207
GO:0038095 Fc-epsilon receptor signaling pathway 2.6516
GO:0050679 positive regulation of epithelial cell proliferation 2.4585
GO:0008543 fibroblast growth factor receptor signaling pathway 2.304
GO:0016337 single organismal cell-cell adhesion 2.091
GO:0045429 positive regulation of nitric oxide biosynthetic process 1.9844
GO:0007173 epidermal growth factor receptor signaling pathway 1.9814
GO:0048015 phosphatidylinositol-mediated signaling 1.8351
GO:0070374 positive regulation of ERK1 and ERK2 cascade 1.7915
GO:0030335 positive regulation of cell migration 1.752
GO:0008284 positive regulation of cell proliferation 1.7256
GO:0045740 positive regulation of DNA replication 1.7214
GO:0000165 MAPK cascade 1.6588
GO:0048011 neurotrophin TRK receptor signaling pathway 1.5523
GO:0045944 positive regulation of transcription from RNA polymerase II promoter 1.4738
GO:0051897 positive regulation of protein kinase B signaling 1.4248
GO:0045087 innate immune response 1.3607
GO:0001503 ossification 1.3518
GO:0042127 regulation of cell proliferation 1.3369
GO:0000902 cell morphogenesis 1.3069
GO:0007411 axon guidance 1.3062
GO:0042327 positive regulation of phosphorylation 1.2798
GO:0008283 cell proliferation 1.2784
GO:0007166 cell surface receptor signaling pathway 1.2541
GO:0001934 positive regulation of protein phosphorylation 1.2453
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway 1.2244
GO:0018108 peptidyl-tyrosine phosphorylation 1.2044
GO:0006950 response to stress 0.9993
GO:0043406 positive regulation of MAP kinase activity 0.9437
GO:0006898 receptor-mediated endocytosis 0.8497
GO:0046777 protein autophosphorylation 0.6626
GO:0007165 signal transduction 0.6552
GO:0007611 learning or memory 0.4789
GO:0043066 negative regulation of apoptotic process 0.4525
GO:0006468 protein phosphorylation 0.4403
GO:0050730 regulation of peptidyl-tyrosine phosphorylation 0.3983
GO:0048146 positive regulation of fibroblast proliferation -0.1378
GO:0007202 activation of phospholipase C activity -0.4722
GO:0071230 cellular response to amino acid stimulus -0.6142
GO:0045739 positive regulation of DNA repair -1.1167
GO:0042177 negative regulation of protein catabolic process -2.1585
GO:0071364 cellular response to epidermal growth factor stimulus -2.4216
GO:0070141 response to UV-A -2.4216
GO:0031659 positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle -2.7017
GO:0050999 regulation of nitric-oxide synthase activity -3.0737
GO:0071392 cellular response to estradiol stimulus -58.7575
GO:0060571 morphogenesis of an epithelial fold -58.7575
GO:0051205 protein insertion into membrane -58.7575
GO:0043006 activation of phospholipase A2 activity by calcium-mediated signaling -58.7575
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway -58.7575
GO:0035413 positive regulation of catenin import into nucleus -58.7575
GO:0021795 cerebral cortex cell migration -58.7575
GO:0007435 salivary gland morphogenesis -58.7575
GO:0001892 embryonic placenta development -58.7575
GO:0008544 epidermis development -58.9639
GO:0001942 hair follicle development -58.9639
Gene Ontology - Molecular Function Log-odds ratio
GO:0004888 transmembrane signaling receptor activity 1.7239
GO:0004716 receptor signaling protein tyrosine kinase activity 1.6268
GO:0004714 transmembrane receptor protein tyrosine kinase activity 1.4307
GO:0030235 nitric-oxide synthase regulator activity 1.3858
GO:0004871 signal transducer activity 1.2126
GO:0042802 identical protein binding 0.9297
GO:0004713 protein tyrosine kinase activity 0.592
GO:0004709 MAP kinase kinase kinase activity 0.499
GO:0031625 ubiquitin protein ligase binding 0.4253
GO:0005515 protein binding 0.2913
GO:0016301 kinase activity 0.0196
GO:0004672 protein kinase activity 0.0196
GO:0005524 ATP binding 0.0021
GO:0016772 transferase activity, transferring phosphorus-containing groups 0.0
GO:0019899 enzyme binding -0.3497
GO:0019903 protein phosphatase binding -0.4139
GO:0051015 actin filament binding -3.2289
GO:0003690 double-stranded DNA binding -58.7575
GO:0005006 epidermal growth factor-activated receptor activity -59.3049
GO:0003682 chromatin binding -59.642
GO:0046982 protein heterodimerization activity -61.2068
Gene Ontology - Cellular Component Log-odds ratio
GO:0045121 membrane raft 2.6931
GO:0009986 cell surface 2.5127
GO:0043235 receptor complex 2.1348
GO:0010008 endosome membrane 1.9666
GO:0048471 perinuclear region of cytoplasm 1.4149
GO:0016021 integral component of membrane 1.4044
GO:0005886 plasma membrane 1.403
GO:0016020 membrane 1.2128
GO:0005634 nucleus 0.4352
GO:0031965 nuclear membrane 0.3858
GO:0005615 extracellular space 0.3722
GO:0031901 early endosome membrane 0.0165
GO:0097489 multivesicular body, internal vesicle lumen 0.0
GO:0030122 AP-2 adaptor complex 0.0
GO:0016323 basolateral plasma membrane -0.1644
GO:0005925 focal adhesion -0.2257
GO:0005737 cytoplasm -0.355
GO:0005768 endosome -1.223
GO:0005789 endoplasmic reticulum membrane -2.5017
GO:0070435 Shc-EGFR complex -58.7575
GO:0005622 intracellular -58.7575
GO:0030139 endocytic vesicle -58.9639
GO:0000139 Golgi membrane -60.1014

The JMOL viwer can load structure PDB files associated to that UniProt protein, as well as models provided by Interactome3D. The SVG image and the sequence scroller bellow correspond to the Ensembl protein associated with that UniProt: ENSP00000275493

In order to adress all inconsistencies between the sequences in UniProt, Ensembl, and UniProt, coordinate maps are built using Smith-Waterman pairwise alignment.

Mark
Clear
Align
ENSP00000275493 Transmembrane ... Low complexity (... Cleavage site (Si... Growth_fac_rcpt_N_dom SSF52058 Kinase-like_dom Superfamily dom... Tyr_kinase_cat_dom Furin_repeat Ser/Thr_dual-sp_kinase_dom SMART domains Ser-Thr/Tyr_kinase_cat_dom Prints domain Furin-like_Cys-rich_dom EGF_rcpt_L Ser-Thr/Tyr_kinase_cat_dom Prot_kinase_dom Pfam domain PS50311 Prot_kinase_dom PROSITE profiles Tyr_kinase_EGF/ERB/XmrK_rcpt PIRSF domain Sequence variant... COSMIC somatic ... 0 200 400 600 800 1000 0 1210 Scale bar Stop gained Frameshift variant Inframe insertion Missense variant Splice region variant Synonymous variant Coding sequence variant Insert Delete Variation Legend
MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLNTVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRVAPQSSEFIGA* _________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________| ________10________20________30________40________50________60________70________80________90_______100_______110_______120_______130_______140_______150_______160_______170_______180_______190_______200_______210_______220_______230_______240_______250_______260_______270_______280_______290_______300_______310_______320_______330_______340_______350_______360_______370_______380_______390_______400_______410_______420_______430_______440_______450_______460_______470_______480_______490_______500_______510_______520_______530_______540_______550_______560_______570_______580_______590_______600_______610_______620_______630_______640_______650_______660_______670_______680_______690_______700_______710_______720_______730_______740_______750_______760_______770_______780_______790_______800_______810_______820_______830_______840_______850_______860_______870_______880_______890_______900_______910_______920_______930_______940_______950_______960_______970_______980_______990______1000______1010______1020______1030______1040______1050______1060______1070______1080______1090______1100______1110______1120______1130______1140______1150______1160______1170______1180______1190______1200______1210

Scroll horizontaly across the sequence

The following information is extracted from Structure-PPi, a workflow for the annotation of protein residues. It finds features overlapping the variant or overlapping any residue that is in close physical proximity to the variant: 5 angstroms spatial distance or adjacent in the sequence if no PDB covers that area.

It may also report protein protein interfaces that might be affected by the variant, i.e. when they are at a distance of 8 angstroms from residues from a partner protein.

The structure PDB files used for these calculations are all those associated with the UniProt protein in UniProt and Interactome3D, which extends this set with models of single proteins and protein-protein interaction complexes. Pairwise alignment is used to resolve any sequence discrepancies.

The databases examined are UniProt, InterPro, COSMIC and Appris. The COSMIC database reports variants affecting that residue, not necessarily the same amino-acid change. Appris agglutinates features from FireDB, which are catalytic sites, and ligand-binding sites, and others such as trans-membrane domains, signal peptides, and ligand binding sites.

Structure-PPi A module for the annotation of cancer-related single-nucleotide variants at protein-protein interfaces. Miguel Vazquez, Alfonso Valencia, Tirso Pons. 2015. Bioinformatics. DOI: 10.1093/bioinformatics/btv142

KinMut Random Forest is a method specific for prediction of the pathogenicity of variants affecting the protein kinase superfamily. It characterizes the variants at the gene, domain and residue level with a combination of general and kinase-specific features. The pathogenicity of variants is evaluated by a random forest algorithm. Predictions are accompanied with a reliability score. Our approach outperforms available methods in a cross-validation experiment on the 3689 kinase variants in Uniprot. (Accuracy: 88.45%, Precision: 81.62%, recall: 75.22%, f-score: 78.29% and MCC: 0.68)

KinMut Random Forest
disease if score >0, neutral if score <0
Score
-0.848
Prediction
neutral

Group log-odds ratio
0.629
Kyte-Doolittle Hydrophobicity
2.6
GO log-odds ratio
-2761.1791
Volume
46.8
C-beta branching
-1
Formal charge
0
FireDB residue
Yes
PhosphoELM residue
No
Uniprot residue
Yes
Active site
No
Binding
No
Carbohydrate
No
Disulfide
No
Metal
No
Modified residue
No
NP Binding
Yes
Repeat
No
Signal
No
Site
No
Trans-membrane
No
Zinc finger
No
Affected protein domains
Domain Log odds ratio
Protein_kinase 0.950917
Other predictors (dbNSFP)
SIFT
disease if score <0.05
Score
0.003
Prediction
disease
Polyphen2_HDIV
possible if >0.453, disease if >0.957
Score
1.0
Prediction
disease
Polyphen2_HVAR
possible if >0.447, disease if >0.909
Score
0.986
Prediction
disease
MutationTaster
disease if score >0.5
Score
1.0
Prediction
disease
MutationAssessor
possible if >1.9, disease if >3.5
Score
1.17
Prediction
neutral
FATHMM
disease if score <-1.5
Score
0.24
Prediction
neutral
VEST3
disease if score >0.8
Score
0.923
Prediction
disease
CADD
disease if score >3.5
Score
2.279366
Prediction
neutral
CADD Kircher (2014) Nature Genetics 46(3):310-5
FATHMM Shihab (2013) Human Mutation 34(1):57-65
VEST3 Carter (2013) BMC Genomics 14(3):1-16
Mutation Assessor Reva (2011) Nucleic Acids Research 1-14
Mutation Taster Schwarz (2014) Nature Methods 11, 361-362
Polyphen2 Adzhubei (2010) Nature Methods 7(4), 248-249
SIFT Ng (2001) Genome Research 11(45), 863-874
These literature co-mentions have been extracted automatically from the literature with iHop. Although it has proved to be a powerful guide to gather contextual information, manual inspection of these results might be required. Refer to Hoffmann and Valencia, 2004 for further details.

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