ID EGFR_HUMAN Reviewed; 1210 AA. AC P00533; O00688; O00732; P06268; Q14225; Q92795; Q9BZS2; Q9GZX1; AC Q9H2C9; Q9H3C9; Q9UMD7; Q9UMD8; Q9UMG5; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 15-JAN-2008, entry version 125. DE Epidermal growth factor receptor precursor (EC 2.7.10.1) (Receptor DE tyrosine-protein kinase ErbB-1). GN Name=EGFR; Synonyms=ERBB1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=84219729; PubMed=6328312; DOI=10.1038/309418a0; RA Ullrich A., Coussens L., Hayflick J.S., Dull T.J., Gray A., Tam A.W., RA Lee J., Yarden Y., Libermann T.A., Schlessinger J., Downward J., RA Mayes E.L.V., Whittle N., Waterfield M.D., Seeburg P.H.; RT "Human epidermal growth factor receptor cDNA sequence and aberrant RT expression of the amplified gene in A431 epidermoid carcinoma cells."; RL Nature 309:418-425(1984). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=95382957; PubMed=7654368; DOI=10.1002/mrd.1080410205; RA Ilekis J.V., Stark B.C., Scoccia B.; RT "Possible role of variant RNA transcripts in the regulation of RT epidermal growth factor receptor expression in human placenta."; RL Mol. Reprod. Dev. 41:149-156(1995). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=97078686; PubMed=8918811; DOI=10.1093/nar/24.20.4050; RA Reiter J.L., Maihle N.J.; RT "A 1.8 kb alternative transcript from the human epidermal growth RT factor receptor gene encodes a truncated form of the receptor."; RL Nucleic Acids Res. 24:4050-4056(1996). RN [4] RP NUCLEOTIDE SEQUENCE (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=97256547; PubMed=9103388; DOI=10.1006/gyno.1996.4526; RA Ilekis J.V., Gariti J., Niederberger C., Scoccia B.; RT "Expression of a truncated epidermal growth factor receptor-like RT protein (TEGFR) in ovarian cancer."; RL Gynecol. Oncol. 65:36-41(1997). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Placenta; RX MEDLINE=21100872; PubMed=11161793; DOI=10.1006/geno.2000.6341; RA Reiter J.L., Threadgill D.W., Eley G.D., Strunk K.E., Danielsen A.J., RA Schehl Sinclair C., Pearsall R.S., Green P.J., Yee D., Lampland A.L., RA Balasubramaniam S., Crossley T.D., Magnuson T.R., James C.D., RA Maihle N.J.; RT "Comparative genomic sequence analysis and isolation of human and RT mouse alternative EGFR transcripts encoding truncated receptor RT isoforms."; RL Genomics 71:1-20(2001). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-98; ARG-266; RP LYS-521; ILE-674; GLY-962 AND PRO-988. RA Livingston R.J., Rieder M.J., Chung M.-W., Ritchie T.K., Olson A.N., RA Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., RA Sherwood J.K., Sherwood A.M., Leithauser B.J., Nickerson D.A.; RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."; RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 575-687. RA Reiter J.L., Threadgill D.W., Danielsen A.J., Schehl C.M., RA Lampland A.L., Balasubramaniam S., Crossley T.O., Magnuson T.R., RA Maihle N.J.; RT "Human and mouse alternative EGFR transcripts encoding only the RT extracellular domain of the receptor."; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 713-924. RX MEDLINE=84196372; PubMed=6326261; RA Lin C.R., Chen W.S., Kruiger W., Stolarsky L.S., Weber W., Evans R.M., RA Verma I.M., Gill G.N., Rosenfeld M.G.; RT "Expression cloning of human EGF receptor complementary DNA: gene RT amplification and three related messenger RNA products in A431 RT cells."; RL Science 224:843-848(1984). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 150-962. RX MEDLINE=84245835; PubMed=6330563; DOI=10.1038/309806a0; RA Xu Y.H., Ishii S., Clark A.J.L., Sullivan M., Wilson R.K., Ma D.P., RA Roe B.A., Merlino G.T., Pastan I.; RT "Human epidermal growth factor receptor cDNA is homologous to a RT variety of RNAs overproduced in A431 carcinoma cells."; RL Nature 309:806-810(1984). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1028-1210. RX MEDLINE=85046483; PubMed=6093780; RA Simmen F.A., Gope M.L., Schulz T.Z., Wright D.A., Carpenter G., RA O'Malley B.W.; RT "Isolation of an evolutionarily conserved epidermal growth factor RT receptor cDNA from human A431 carcinoma cells."; RL Biochem. Biophys. Res. Commun. 124:125-132(1984). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29. RX MEDLINE=88217333; PubMed=3329716; RA Haley J.D., Whittle N., Bennett P., Kinchington D., Ullrich A., RA Waterfield M.D.; RT "The human EGF receptor gene: structure of the 110 kb locus and RT identification of sequences regulating its transcription."; RL Oncogene Res. 1:375-396(1987). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29. RX MEDLINE=91107677; PubMed=1988448; RA Haley J.D., Waterfield M.D.; RT "Contributory effects of de novo transcription and premature RT transcript termination in the regulation of human epidermal growth RT factor receptor proto-oncogene RNA synthesis."; RL J. Biol. Chem. 266:1746-1753(1991). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29. RX MEDLINE=85270438; PubMed=2991899; RA Ishii S., Xu Y.H., Stratton R.H., Roe B.A., Merlino G.T., Pastan I.; RT "Characterization and sequence of the promoter region of the human RT epidermal growth factor receptor gene."; RL Proc. Natl. Acad. Sci. U.S.A. 82:4920-4924(1985). RN [14] RP NUCLEOTIDE SEQUENCE OF 25-49. RX MEDLINE=84172183; PubMed=6324343; RA Weber W., Gill G.N., Spiess J.; RT "Production of an epidermal growth factor receptor-related protein."; RL Science 224:294-297(1984). RN [15] RP PROTEIN SEQUENCE OF 540. RA Kohda D.; RL Submitted (SEP-1997) to UniProtKB. RN [16] RP PROTEIN SEQUENCE OF 687-705; 986-998; 1000-1023; 1026-1030 AND RP 1068-1077, AND PHOSPHORYLATION AT THR-693; SER-695; SER-1070 AND RP SER-1071. RX MEDLINE=88330814; PubMed=3138233; RA Heisermann G.J., Gill G.N.; RT "Epidermal growth factor receptor threonine and serine residues RT phosphorylated in vivo."; RL J. Biol. Chem. 263:13152-13158(1988). RN [17] RP PROTEIN SEQUENCE OF 25-39. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [18] RP PROTEIN SEQUENCE OF 740-744 AND 746-747. RX MEDLINE=85182650; PubMed=2985580; RA Russo M.W., Lukas T.J., Cohen S., Staros J.V.; RT "Identification of residues in the nucleotide binding site of the RT epidermal growth factor receptor/kinase."; RL J. Biol. Chem. 260:5205-5208(1985). RN [19] RP PROTEIN SEQUENCE OF 861-875 AND 914-932, UBIQUITINATION AT LYS-716; RP LYS-737; LYS-754; LYS-867; LYS-929 AND LYS-970, AND MASS SPECTROMETRY. RX PubMed=16543144; DOI=10.1016/j.molcel.2006.02.018; RA Huang F., Kirkpatrick D., Jiang X., Gygi S., Sorkin A.; RT "Differential regulation of EGF receptor internalization and RT degradation by multiubiquitination within the kinase domain."; RL Mol. Cell 21:737-748(2006). RN [20] RP PARTIAL PROTEIN SEQUENCE, AND DISULFIDE BONDS. RX MEDLINE=98225196; PubMed=9556602; DOI=10.1074/jbc.273.18.11150; RA Abe Y., Odaka M., Inagaki F., Lax I., Schlessinger J., Kohda D.; RT "Disulfide bond structure of human epidermal growth factor receptor."; RL J. Biol. Chem. 273:11150-11157(1998). RN [21] RP RECEPTOR ACTIVITY. RX MEDLINE=84191554; PubMed=6325948; DOI=10.1038/309270a0; RA Mroczkowski B., Mosig G., Cohen S.; RT "ATP-stimulated interaction between epidermal growth factor receptor RT and supercoiled DNA."; RL Nature 309:270-273(1984). RN [22] RP REVIEW. RX MEDLINE=87297456; PubMed=3039909; RX DOI=10.1146/annurev.bi.56.070187.004313; RA Carpenter G.; RT "Receptors for epidermal growth factor and other polypeptide RT mitogens."; RL Annu. Rev. Biochem. 56:881-914(1987). RN [23] RP LIGAND-BINDING. RX MEDLINE=90003233; PubMed=2790960; DOI=10.1016/0092-8674(89)90867-2; RA Chen W.S., Lazar C.S., Lund K.A., Welsh J.B., Chang C.P., Walton G.M., RA Der C.J., Wiley H.S., Gill G.N., Rosenfeld M.G.; RT "Functional independence of the epidermal growth factor receptor from RT a domain required for ligand-induced internalization and calcium RT regulation."; RL Cell 59:33-43(1989). RN [24] RP PHOSPHORYLATION. RX MEDLINE=89278137; PubMed=2543678; RA Margolis B.L., Lax I., Kris R., Dombalagian M., Honegger A.M., RA Howk R., Givol D., Ullrich A., Schlessinger J.; RT "All autophosphorylation sites of epidermal growth factor (EGF) RT receptor and HER2/neu are located in their carboxyl-terminal tails. RT Identification of a novel site in EGF receptor."; RL J. Biol. Chem. 264:10667-10671(1989). RN [25] RP INTERACTION WITH CBL. RX PubMed=7657591; DOI=10.1074/jbc.270.35.20242; RA Galisteo M.L., Dikic I., Batzer A.G., Langdon W.Y., Schlessinger J.; RT "Tyrosine phosphorylation of the c-cbl proto-oncogene protein product RT and association with epidermal growth factor (EGF) receptor upon EGF RT stimulation."; RL J. Biol. Chem. 270:20242-20245(1995). RN [26] RP GLYCOSYLATION AT ASN-128; ASN-175; ASN-413; ASN-444 AND ASN-528. RX MEDLINE=96398132; PubMed=8962717; RA Smith K.D., Davies M.J., Bailey D., Renouf D.V., Hounsell E.F.; RT "Analysis of the glycosylation patterns of the extracellular domain of RT the epidermal growth factor receptor expressed in Chinese hamster RT ovary fibroblasts."; RL Growth Factors 13:121-132(1996). RN [27] RP GLYCOSYLATION AT ASN-56; ASN-352; ASN-361; ASN-568 AND ASN-603. RX MEDLINE=20198209; PubMed=10731668; RA Sato C., Kim J.-H., Abe Y., Saito K., Yokoyama S., Kohda D.; RT "Characterization of the N-oligosaccharides attached to the atypical RT Asn-X-Cys sequence of recombinant human epidermal growth factor RT receptor."; RL J. Biochem. 127:65-72(2000). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [29] RP IDENTIFICATION IN A COMPLEX WITH PIK3C2A AND ERBB2, IDENTIFICATION IN RP A COMPLEX WITH PIK3C2B AND ERBB2, INTERACTION WITH PIK3C2B, AND RP MUTAGENESIS OF TYR-1016; TYR-1092; TYR-1110; TYR-1172 AND TYR-1197. RX PubMed=10805725; DOI=10.1128/MCB.20.11.3817-3830.2000; RA Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D., RA Domin J.; RT "Class II phosphoinositide 3-kinases are downstream targets of RT activated polypeptide growth factor receptors."; RL Mol. Cell. Biol. 20:3817-3830(2000). RN [30] RP INTERACTION WITH RIPK1. RX MEDLINE=21153697; PubMed=11116146; DOI=10.1074/jbc.M008458200; RA Habib A.A., Chatterjee S., Park S.-K., Ratan R.R., Lefebvre S., RA Vartanian T.; RT "The epidermal growth factor receptor engages receptor interacting RT protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to RT activate NF-kappa B. Identification of a novel receptor-tyrosine RT kinase signalosome."; RL J. Biol. Chem. 276:8865-8874(2001). RN [31] RP GLYCOSYLATION AT ASN-56; ASN-128; ASN-175; ASN-196; ASN-352; ASN-361; RP ASN-413; ASN-444; ASN-528; ASN-568 AND ASN-603, PHOSPHORYLATION AT RP THR-693; SER-991 AND SER-1026, AND MASS SPECTROMETRY. RX PubMed=16083266; DOI=10.1021/pr050113n; RA Wu S.L., Kim J., Hancock W.S., Karger B.; RT "Extended Range Proteomic Analysis (ERPA): a new and sensitive LC-MS RT platform for high sequence coverage of complex proteins with extensive RT post-translational modifications-comprehensive analysis of beta-casein RT and epidermal growth factor receptor (EGFR)."; RL J. Proteome Res. 4:1155-1170(2005). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-998; TYR-1069; TYR-1092; RP SER-1166 AND TYR-1172, AND MASS SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=15951569; DOI=10.1074/mcp.M500089-MCP200; RA Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., RA Lauffenburger D.A., White F.M.; RT "Time-resolved mass spectrometry of tyrosine phosphorylation sites in RT the epidermal growth factor receptor signaling network reveals dynamic RT modules."; RL Mol. Cell. Proteomics 4:1240-1250(2005). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-978, AND MASS RP SPECTROMETRY. RC TISSUE=Hepatocyte; RX PubMed=16097034; DOI=10.1002/pmic.200401217; RA Gevaert K., Staes A., Van Damme J., De Groot S., Hugelier K., RA Demol H., Martens L., Goethals M., Vandekerckhove J.; RT "Global phosphoproteome analysis on human HepG2 hepatocytes using RT reversed-phase diagonal LC."; RL Proteomics 5:3589-3599(2005). RN [34] RP INTERACTION WITH PELP1. RX PubMed=16140940; DOI=10.1158/0008-5472.CAN-05-0614; RA Vadlamudi R.K., Manavathi B., Balasenthil S., Nair S.S., Yang Z., RA Sahin A.A., Kumar R.; RT "Functional implications of altered subcellular localization of PELP1 RT in breast cancer cells."; RL Cancer Res. 65:7724-7732(2005). RN [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693; SER-991; SER-995; RP TYR-998; SER-1064; TYR-1069; TYR-1092; TYR-1110; TYR-1138; TYR-1172 RP AND TYR-1197, AND MASS SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693, AND MASS RP SPECTROMETRY. RX PubMed=17192257; DOI=10.1074/mcp.T600062-MCP200; RA Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., RA Keri G., Wehland J., Daub H.; RT "Proteomics analysis of protein kinases by target class-selective RT prefractionation and tandem mass spectrometry."; RL Mol. Cell. Proteomics 6:537-547(2007). RN [37] RP VARIANTS LUNG CANCER SER-719 AND ARG-858. RX PubMed=15118125; DOI=10.1126/science.1099314; RA Paez J.G., Janne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., RA Herman P., Kaye F.J., Lindeman N., Boggon T.J., Naoki K., Sasaki H., RA Fujii Y., Eck M.J., Sellers W.R., Johnson B.E., Meyerson M.; RT "EGFR mutations in lung cancer: correlation with clinical response to RT gefitinib therapy."; RL Science 304:1497-1500(2004). RN [38] RP VARIANTS LUNG CANCER ALA-709; LYS-709; ALA-719; ASP-719; CYS-719; RP SER-719; SER-724; LYS-734; GLU-746 DEL; PHE-747; 747-LEU--GLU-749 DEL; RP PRO-748; 752-SER--ILE-759 DEL; ARG-787; MET-790; VAL-833; LEU-834; RP MET-858; ARG-858; GLN-861 AND GLU-873. RX PubMed=16533793; DOI=10.1158/1078-0432.CCR-05-1981; RA Tam I.Y.S., Chung L.P., Suen W.S., Wang E., Wong M.C.M., Ho K.K., RA Lam W.K., Chiu S.W., Girard L., Minna J.D., Gazdar A.F., Wong M.P.; RT "Distinct epidermal growth factor receptor and KRAS mutation patterns RT in non-small cell lung cancer patients with different tobacco exposure RT and clinicopathologic features."; RL Clin. Cancer Res. 12:1647-1653(2006). CC -!- FUNCTION: Receptor for EGF, but also for other members of the EGF CC family, as TGF-alpha, amphiregulin, betacellulin, heparin-binding CC EGF-like growth factor, GP30 and vaccinia virus growth factor. Is CC involved in the control of cell growth and differentiation. CC -!- FUNCTION: Isoform 2/truncated isoform may act as an antagonist. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- SUBUNIT: Binds RIPK1. CBL interacts with the autophosphorylated C- CC terminal tail of the EGF receptor. Part of a complex with ERBB2 CC and either PIK3C2A or PIK3C2B. The autophosphorylated form CC interacts with PIK3C2B, maybe indirectly. Interacts with PELP1. CC -!- INTERACTION: CC Self; NbExp=1; IntAct=EBI-297353, EBI-297353; CC Q29376:- (xeno); NbExp=1; IntAct=EBI-297353, EBI-1256881; CC P62157:CALM (xeno); NbExp=1; IntAct=EBI-297353, EBI-397403; CC P62158:CALM1; NbExp=1; IntAct=EBI-297353, EBI-397435; CC P62161:Calm1 (xeno); NbExp=2; IntAct=EBI-297353, EBI-397530; CC P62204:Calm1 (xeno); NbExp=1; IntAct=EBI-297353, EBI-397460; CC P22681:CBL; NbExp=1; IntAct=EBI-297353, EBI-518228; CC P22682:Cbl (xeno); NbExp=1; IntAct=EBI-297353, EBI-640919; CC P13987:CD59; NbExp=1; IntAct=EBI-297353, EBI-297972; CC P01133:EGF; NbExp=2; IntAct=EBI-297353, EBI-640857; CC P04626:ERBB2; NbExp=2; IntAct=EBI-297353, EBI-641062; CC P21860:ERBB3; NbExp=2; IntAct=EBI-297353, EBI-720706; CC Q15303:ERBB4; NbExp=2; IntAct=EBI-297353, EBI-80371; CC P62993:GRB2; NbExp=2; IntAct=EBI-297353, EBI-401755; CC O00750:PIK3C2B; NbExp=4; IntAct=EBI-297353, EBI-641107; CC Q9UJ41:RABGEF1; NbExp=2; IntAct=EBI-297353, EBI-913954; CC P98083:Shc1 (xeno); NbExp=1; IntAct=EBI-297353, EBI-300201; CC P63104:YWHAZ; NbExp=1; IntAct=EBI-297353, EBI-347088; CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein. CC -!- SUBCELLULAR LOCATION: Isoform 2: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=p170; CC IsoId=P00533-1; Sequence=Displayed; CC Name=2; Synonyms=p60, Truncated, TEGFR; CC IsoId=P00533-2; Sequence=VSP_002887, VSP_002888; CC Name=3; Synonyms=p110; CC IsoId=P00533-3; Sequence=VSP_002889, VSP_002890; CC Name=4; CC IsoId=P00533-4; Sequence=VSP_002891, VSP_002892; CC -!- TISSUE SPECIFICITY: Expressed in placenta. Isoform 2 is also CC expressed in ovarian cancers. CC -!- PTM: Phosphorylation of Ser-695 is partial and occurs only if Thr- CC 693 is phosphorylated. CC -!- PTM: Monoubiquitinated and polyubiquitinated upon EGF stimulation; CC which does not affect tyrosine kinase activity or signaling CC capacity but may play a role in lysosomal targeting. Polyubiquitin CC linkage is mainly through 'Lys-63', but linkage through 'Lys-48', CC 'Lys-11' and 'Lys-29' also occur. CC -!- DISEASE: Defects in EGFR are associated with lung cancer CC [MIM:211980]. CC -!- MISCELLANEOUS: Binding of EGF to the receptor leads to CC dimerization, internalization of the EGF-receptor complex, CC induction of the tyrosine kinase activity, stimulation of cell DNA CC synthesis, and cell proliferation. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. EGF receptor subfamily. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=EGFR"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=EGFR entry; CC URL="http://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X00588; CAA25240.1; -; mRNA. DR EMBL; U95089; AAB53063.1; -; mRNA. DR EMBL; U48722; AAC50802.1; -; mRNA. DR EMBL; U48723; AAC50804.1; -; Genomic_DNA. DR EMBL; U48724; AAC50796.1; -; Genomic_RNA. DR EMBL; U48725; AAC50797.1; -; Genomic_RNA. DR EMBL; U48726; AAC50798.1; -; Genomic_RNA. DR EMBL; U48727; AAC50799.1; -; Genomic_RNA. DR EMBL; U48728; AAC50800.1; -; Genomic_RNA. DR EMBL; U48729; AAC50801.1; -; Genomic_RNA. DR EMBL; AF288738; AAG35786.1; -; Genomic_DNA. DR EMBL; AF288738; AAG35787.1; -; Genomic_DNA. DR EMBL; AF288738; AAG35788.1; -; Genomic_DNA. DR EMBL; AF288738; AAG35789.1; -; Genomic_DNA. DR EMBL; AF288738; AAG35790.1; -; Genomic_DNA. DR EMBL; AY588246; AAS83109.1; -; Genomic_DNA. DR EMBL; AF277897; AAK01080.1; -; mRNA. DR EMBL; AF125253; AAG43240.1; -; mRNA. DR EMBL; AF125539; AAG43243.1; -; Genomic_DNA. DR EMBL; AF125538; AAG43243.1; JOINED; Genomic_DNA. DR EMBL; X06370; CAA29668.1; -; Genomic_DNA. DR EMBL; X00663; CAA25282.1; -; mRNA. DR EMBL; M38425; AAA63171.1; -; Genomic_DNA. DR EMBL; M11234; AAA52370.1; -; Genomic_DNA. DR PIR; A00641; GQHUE. DR RefSeq; NP_005219.2; -. DR UniGene; Hs.488293; -. DR PDB; 1DNQ; Model; -; A=25-336. DR PDB; 1DNR; Model; -; A=337-645. DR PDB; 1IVO; X-ray; 3.30 A; A/B=25-646. DR PDB; 1M14; X-ray; 2.60 A; A=695-1022. DR PDB; 1M17; X-ray; 2.60 A; A=695-1022. DR PDB; 1MOX; X-ray; 2.50 A; A/B=25-525. DR PDB; 1NQL; X-ray; 2.80 A; A=25-642. DR PDB; 1XKK; X-ray; 2.40 A; A=695-1022. DR PDB; 1YY9; X-ray; 2.60 A; A=25-642. DR PDB; 1Z9I; NMR; -; A=669-721. DR PDB; 2EXP; Model; -; A=311-326. DR PDB; 2GS2; X-ray; 2.80 A; A=696-1022. DR PDB; 2GS7; X-ray; 2.60 A; A/B=696-1022. DR PDB; 2ITN; X-ray; 2.47 A; A=696-1022. DR PDB; 2ITO; X-ray; 3.25 A; A=696-1022. DR PDB; 2ITP; X-ray; 2.74 A; A=696-1022. DR PDB; 2ITQ; X-ray; 2.68 A; A=696-1022. DR PDB; 2ITT; X-ray; 2.73 A; A=696-1022. DR PDB; 2ITU; X-ray; 2.80 A; A=696-1022. DR PDB; 2ITV; X-ray; 2.47 A; A=696-1022. DR PDB; 2ITW; X-ray; 2.88 A; A=696-1022. DR PDB; 2ITX; X-ray; 2.98 A; A=696-1022. DR PDB; 2ITY; X-ray; 3.42 A; A=696-1022. DR PDB; 2ITZ; X-ray; 2.80 A; A=696-1022. DR PDB; 2J5E; X-ray; 3.10 A; A=696-1022. DR PDB; 2J6M; X-ray; 3.10 A; A=696-1022. DR PDBsum; 1DNQ; -. DR PDBsum; 1DNR; -. DR PDBsum; 1IVO; -. DR PDBsum; 1M14; -. DR PDBsum; 1M17; -. DR PDBsum; 1MOX; -. DR PDBsum; 1NQL; -. DR PDBsum; 1XKK; -. DR PDBsum; 1YY9; -. DR PDBsum; 1Z9I; -. DR PDBsum; 2EXP; -. DR PDBsum; 2GS2; -. DR PDBsum; 2GS7; -. DR PDBsum; 2ITN; -. DR PDBsum; 2ITO; -. DR PDBsum; 2ITP; -. DR PDBsum; 2ITQ; -. DR PDBsum; 2ITT; -. DR PDBsum; 2ITU; -. DR PDBsum; 2ITV; -. DR PDBsum; 2ITW; -. DR PDBsum; 2ITX; -. DR PDBsum; 2ITY; -. DR PDBsum; 2ITZ; -. DR PDBsum; 2J5E; -. DR PDBsum; 2J6M; -. DR DisProt; DP00309; -. DR DIP; DIP:405N; -. DR IntAct; P00533; -. DR GlycoSuiteDB; P00533; -. DR SWISS-2DPAGE; P00533; HUMAN. DR PeptideAtlas; P00533; -. DR Ensembl; ENSG00000146648; Homo sapiens. DR GeneID; 1956; -. DR KEGG; hsa:1956; -. DR H-InvDB; HIX0025274; -. DR H-InvDB; HIX0025338; -. DR HGNC; HGNC:3236; EGFR. DR HPA; CAB000035; -. DR HPA; HPA001200; -. DR MIM; 131550; gene. DR MIM; 211980; phenotype. DR Orphanet; 360; Glioblastoma. DR PharmGKB; PA7360; -. DR Reactome; REACT_9417; Signaling by EGFR. DR DrugBank; BTD00071; Cetuximab. DR DrugBank; APRD00951; Erlotinib. DR DrugBank; APRD00997; Gefitinib. DR LinkHub; P00533; -. DR ArrayExpress; P00533; -. DR CleanEx; HS_EGFR; -. DR GermOnline; ENSG00000146648; Homo sapiens. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; NAS:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HGNC. DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; NAS:UniProtKB. DR GO; GO:0005006; F:epidermal growth factor receptor activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004710; F:MAP/ERK kinase kinase activity; NAS:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0043006; P:calcium-dependent phospholipase A2 activation; TAS:UniProtKB. DR GO; GO:0016337; P:cell-cell adhesion; IMP:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling ...; IDA:UniProtKB. DR GO; GO:0001503; P:ossification; NAS:UniProtKB. DR GO; GO:0007202; P:phospholipase C activation; TAS:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell prol...; IDA:UniProtKB. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynt...; IDA:UniProtKB. DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:UniProtKB. DR GO; GO:0051205; P:protein insertion into membrane; TAS:UniProtKB. DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; IDA:UniProtKB. DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphoryla...; IMP:UniProtKB. DR GO; GO:0006950; P:response to stress; NAS:UniProtKB. DR InterPro; IPR000494; EGF_rcpt_L. DR InterPro; IPR006211; Furin-like. DR InterPro; IPR006212; Furin_repeat. DR InterPro; IPR000719; Prot_kinase_core. DR InterPro; IPR001245; Tyr_pkinase. DR InterPro; IPR008266; Tyr_pkinase_AS. DR Pfam; PF00757; Furin-like; 1. DR Pfam; PF07714; Pkinase_Tyr; 1. DR Pfam; PF01030; Recep_L_domain; 2. DR PRINTS; PR00109; TYRKINASE. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00261; FU; 3. DR SMART; SM00219; TyrKc; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Anti-oncogene; ATP-binding; KW Cell cycle; Direct protein sequencing; Disease mutation; Glycoprotein; KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; KW Receptor; Repeat; Secreted; Signal; Transferase; Transmembrane; KW Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1 24 FT CHAIN 25 1210 Epidermal growth factor receptor. FT /FTId=PRO_0000016665. FT TOPO_DOM 25 645 Extracellular (Potential). FT TRANSMEM 646 668 Potential. FT TOPO_DOM 669 1210 Cytoplasmic (Potential). FT REPEAT 75 300 Approximate. FT REPEAT 390 600 Approximate. FT DOMAIN 712 979 Protein kinase. FT NP_BIND 718 726 ATP (By similarity). FT COMPBIAS 1025 1071 Ser-rich. FT ACT_SITE 837 837 Proton acceptor (By similarity). FT BINDING 745 745 ATP (By similarity). FT SITE 1016 1016 Important for interaction with PIK3C2B. FT MOD_RES 678 678 Phosphothreonine; by PKC. FT MOD_RES 693 693 Phosphothreonine. FT MOD_RES 695 695 Phosphoserine. FT MOD_RES 978 978 Phosphotyrosine. FT MOD_RES 991 991 Phosphoserine. FT MOD_RES 995 995 Phosphoserine. FT MOD_RES 998 998 Phosphotyrosine. FT MOD_RES 1026 1026 Phosphoserine. FT MOD_RES 1064 1064 Phosphoserine. FT MOD_RES 1069 1069 Phosphotyrosine. FT MOD_RES 1070 1070 Phosphoserine. FT MOD_RES 1071 1071 Phosphoserine. FT MOD_RES 1092 1092 Phosphotyrosine; by autocatalysis. FT MOD_RES 1110 1110 Phosphotyrosine; by autocatalysis. FT MOD_RES 1138 1138 Phosphotyrosine. FT MOD_RES 1166 1166 Phosphoserine. FT MOD_RES 1172 1172 Phosphotyrosine; by autocatalysis. FT MOD_RES 1197 1197 Phosphotyrosine; by autocatalysis. FT CARBOHYD 56 56 N-linked (GlcNAc...) (complex); atypical; FT partial. FT /FTId=CAR_000227. FT CARBOHYD 128 128 N-linked (GlcNAc...). FT CARBOHYD 175 175 N-linked (GlcNAc...). FT CARBOHYD 196 196 N-linked (GlcNAc...). FT CARBOHYD 352 352 N-linked (GlcNAc...). FT CARBOHYD 361 361 N-linked (GlcNAc...). FT CARBOHYD 413 413 N-linked (GlcNAc...). FT CARBOHYD 444 444 N-linked (GlcNAc...). FT CARBOHYD 528 528 N-linked (GlcNAc...). FT CARBOHYD 568 568 N-linked (GlcNAc...); partial. FT CARBOHYD 603 603 N-linked (GlcNAc...); partial. FT DISULFID 190 199 FT DISULFID 194 207 FT DISULFID 215 223 FT DISULFID 219 231 FT DISULFID 232 240 FT DISULFID 236 248 FT DISULFID 251 260 FT DISULFID 264 291 FT DISULFID 295 307 FT DISULFID 311 326 FT DISULFID 329 333 FT DISULFID 506 515 FT DISULFID 510 523 FT DISULFID 526 535 FT DISULFID 539 555 FT DISULFID 558 571 FT DISULFID 562 579 FT DISULFID 582 591 FT DISULFID 595 617 FT DISULFID 620 628 FT DISULFID 624 636 FT CROSSLNK 716 716 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT CROSSLNK 737 737 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT CROSSLNK 754 754 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT CROSSLNK 867 867 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT CROSSLNK 929 929 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT CROSSLNK 970 970 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT VAR_SEQ 404 405 FL -> LS (in isoform 2). FT /FTId=VSP_002887. FT VAR_SEQ 406 1210 Missing (in isoform 2). FT /FTId=VSP_002888. FT VAR_SEQ 628 705 CTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM FT RRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLR -> FT PGNESLKAMLFCLFKLSSCNQSNDGSVSHQSGSPAAQESCL FT GWIPSLLPSEFQLGWGGCSHLHAWPSASVIITASSCH (in FT isoform 3). FT /FTId=VSP_002889. FT VAR_SEQ 628 628 C -> S (in isoform 4). FT /FTId=VSP_002891. FT VAR_SEQ 629 1210 Missing (in isoform 4). FT /FTId=VSP_002892. FT VAR_SEQ 706 1210 Missing (in isoform 3). FT /FTId=VSP_002890. FT VARIANT 98 98 R -> Q (in dbSNP:rs17289589). FT /FTId=VAR_019293. FT VARIANT 266 266 P -> R (in dbSNP:rs17336639). FT /FTId=VAR_019294. FT VARIANT 521 521 R -> K (in dbSNP:rs11543848). FT /FTId=VAR_019295. FT VARIANT 674 674 V -> I (in dbSNP:rs17337079). FT /FTId=VAR_019296. FT VARIANT 709 709 E -> A (in lung cancer). FT /FTId=VAR_026084. FT VARIANT 709 709 E -> K (in lung cancer). FT /FTId=VAR_026085. FT VARIANT 719 719 G -> A (in lung cancer). FT /FTId=VAR_026086. FT VARIANT 719 719 G -> C (in lung cancer; FT dbSNP:rs28929495). FT /FTId=VAR_026087. FT VARIANT 719 719 G -> D (in lung cancer). FT /FTId=VAR_026088. FT VARIANT 719 719 G -> S (in lung cancer; somatic FT mutation). FT /FTId=VAR_019297. FT VARIANT 724 724 G -> S (in lung cancer). FT /FTId=VAR_026089. FT VARIANT 734 734 E -> K (in lung cancer). FT /FTId=VAR_026090. FT VARIANT 746 750 Missing (in lung cancer). FT /FTId=VAR_026092. FT VARIANT 746 746 Missing (in lung cancer). FT /FTId=VAR_026091. FT VARIANT 747 749 Missing (in lung cancer). FT /FTId=VAR_026094. FT VARIANT 747 747 L -> F (in lung cancer). FT /FTId=VAR_026093. FT VARIANT 748 748 R -> P (in lung cancer). FT /FTId=VAR_026095. FT VARIANT 752 759 Missing (in lung cancer). FT /FTId=VAR_026096. FT VARIANT 787 787 Q -> R (in lung cancer). FT /FTId=VAR_026097. FT VARIANT 790 790 T -> M (in lung cancer). FT /FTId=VAR_026098. FT VARIANT 833 833 L -> V (in lung cancer). FT /FTId=VAR_026099. FT VARIANT 834 834 V -> L (in lung cancer). FT /FTId=VAR_026100. FT VARIANT 858 858 L -> M (in lung cancer). FT /FTId=VAR_026101. FT VARIANT 858 858 L -> R (in lung cancer; somatic FT mutation). FT /FTId=VAR_019298. FT VARIANT 861 861 L -> Q (in lung cancer). FT /FTId=VAR_026102. FT VARIANT 873 873 G -> E (in lung cancer). FT /FTId=VAR_026103. FT VARIANT 962 962 R -> G (in dbSNP:rs17337451). FT /FTId=VAR_019299. FT VARIANT 988 988 H -> P (in dbSNP:rs17290699). FT /FTId=VAR_019300. FT MUTAGEN 1016 1016 Y->F: 50% decrease in interaction with FT PIK3C2B. 65% decrease in interaction with FT PIK3C2B; when associated with F-1197. FT Abolishes interaction with PIK3C2B; when FT associated with F-1197 and F-1092. FT MUTAGEN 1092 1092 Y->F: No change in interaction with FT PIK3C2B. Abolishes interaction with FT PIK3C2B; when associated with F-1197 and FT F-1016. FT MUTAGEN 1110 1110 Y->F: No change in interaction with FT PIK3C2B. FT MUTAGEN 1172 1172 Y->F: No change in interaction with FT PIK3C2B. FT MUTAGEN 1197 1197 Y->F: No change in interaction with FT PIK3C2B. 65% decrease in interaction with FT PIK3C2B; when associated with F-1016. FT Abolishes interaction with PIK3C2B; when FT associated with F-1092 and F-1016. FT CONFLICT 540 540 N -> K (in Ref. 1). FT STRAND 40 43 FT HELIX 44 55 FT STRAND 59 63 FT STRAND 65 67 FT HELIX 77 81 FT STRAND 84 87 FT STRAND 89 93 FT HELIX 101 103 FT TURN 114 116 FT STRAND 117 122 FT STRAND 145 152 FT HELIX 159 161 FT TURN 164 167 FT TURN 173 175 FT STRAND 195 197 FT STRAND 200 202 FT TURN 203 205 FT STRAND 211 215 FT STRAND 224 229 FT STRAND 236 238 FT STRAND 241 247 FT STRAND 249 256 FT STRAND 259 263 FT STRAND 267 271 FT TURN 272 275 FT STRAND 276 279 FT STRAND 285 287 FT STRAND 290 294 FT STRAND 299 301 FT STRAND 305 309 FT STRAND 321 323 FT STRAND 330 332 FT STRAND 340 342 FT HELIX 343 345 FT HELIX 353 355 FT HELIX 357 359 FT STRAND 363 367 FT STRAND 369 371 FT HELIX 373 377 FT TURN 380 383 FT HELIX 389 397 FT STRAND 400 403 FT STRAND 405 408 FT HELIX 418 420 FT TURN 433 435 FT STRAND 436 442 FT STRAND 458 464 FT HELIX 472 474 FT HELIX 477 480 FT STRAND 492 494 FT HELIX 496 498 FT TURN 499 503 FT TURN 507 509 FT STRAND 515 519 FT STRAND 522 525 FT STRAND 671 673 FT HELIX 678 684 FT HELIX 685 687 FT STRAND 688 692 FT STRAND 694 697 FT STRAND 704 706 FT TURN 709 711 FT STRAND 712 720 FT STRAND 722 731 FT STRAND 740 747 FT HELIX 756 768 FT STRAND 777 791 FT HELIX 798 804 FT STRAND 806 808 FT HELIX 811 830 FT HELIX 840 842 FT STRAND 843 847 FT STRAND 850 853 FT HELIX 858 861 FT TURN 862 865 FT TURN 878 880 FT HELIX 883 888 FT HELIX 893 908 FT TURN 914 917 FT HELIX 920 922 FT HELIX 923 929 FT HELIX 941 950 FT HELIX 955 957 FT HELIX 961 973 FT HELIX 975 978 FT TURN 982 986 FT HELIX 996 1002 FT HELIX 1013 1016 SQ SEQUENCE 1210 AA; 134277 MW; D8A2A50B4EFB6ED2 CRC64; MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN LLEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCPTNG PKIPSIATGM VGALLLLLVV ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEAPN QALLRILKET EFKKIKVLGS GAFGTVYKGL WIPEGEKVKI PVAIKELREA TSPKANKEIL DEAYVMASVD NPHVCRLLGI CLTSTVQLIT QLMPFGCLLD YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA RNVLVKTPQH VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY GVTVWELMTF GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC WMIDADSRPK FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA LMDEEDMDDV VDADEYLIPQ QGFFSSPSTS RTPLLSSLSA TSNNSTVACI DRNGLQSCPI KEDSFLQRYS SDPTGALTED SIDDTFLPVP EYINQSVPKR PAGSVQNPVY HNQPLNPAPS RDPHYQDPHS TAVGNPEYLN TVQPTCVNST FDSPAHWAQK GSHQISLDNP DYQQDFFPKE AKPNGIFKGS TAENAEYLRV APQSSEFIGA //