ID EGFR_HUMAN Reviewed; 1210 AA. AC P00533; O00688; O00732; P06268; Q14225; Q68GS5; 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 27-MAR-2024, entry version 291. DE RecName: Full=Epidermal growth factor receptor {ECO:0000305}; DE EC=2.7.10.1; DE AltName: Full=Proto-oncogene c-ErbB-1; DE AltName: Full=Receptor tyrosine-protein kinase erbB-1; DE Flags: Precursor; GN Name=EGFR {ECO:0000312|HGNC:HGNC:3236}; Synonyms=ERBB, ERBB1, HER1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 25-32. RX 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 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 epidermal RT 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 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 factor RT receptor gene encodes a truncated form of the receptor."; RL Nucleic Acids Res. 24:4050-4056(1996). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX 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 protein RT (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 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., Maihle N.J.; RT "Comparative genomic sequence analysis and isolation of human and mouse RT alternative EGFR transcripts encoding truncated receptor isoforms."; RL Genomics 71:1-20(2001). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Xu L., Hong A., He X.; RT "Cloning of the cDNA for a short EGF receptor from human placenta."; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-98; ARG-266; LYS-521; RP ILE-674; GLY-962 AND PRO-988. RG NIEHS SNPs program; RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 575-687. RA Reiter J.L., Threadgill D.W., Danielsen A.J., Schehl C.M., Lampland A.L., RA Balasubramaniam S., Crossley T.O., Magnuson T.R., 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 713-924. RX PubMed=6326261; DOI=10.1126/science.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 cells."; RL Science 224:843-848(1984). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 150-962. RX 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 variety of RT RNAs overproduced in A431 carcinoma cells."; RL Nature 309:806-810(1984). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1028-1210. RX PubMed=6093780; DOI=10.1016/0006-291x(84)90926-4; 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 receptor RT cDNA from human A431 carcinoma cells."; RL Biochem. Biophys. Res. Commun. 124:125-132(1984). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29. RX 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 [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29. RX PubMed=1988448; DOI=10.1016/s0021-9258(18)52359-0; RA Haley J.D., Waterfield M.D.; RT "Contributory effects of de novo transcription and premature transcript RT termination in the regulation of human epidermal growth factor receptor RT proto-oncogene RNA synthesis."; RL J. Biol. Chem. 266:1746-1753(1991). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29. RX PubMed=2991899; DOI=10.1073/pnas.82.15.4920; 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 [15] RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-49. RX PubMed=6324343; DOI=10.1126/science.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 [16] RP PROTEIN SEQUENCE OF 540. RA Kohda D.; RL Submitted (SEP-1997) to UniProtKB. RN [17] RP PROTEIN SEQUENCE OF 687-705; 986-998; 1000-1023; 1026-1030 AND 1068-1077, RP AND PHOSPHORYLATION AT THR-693; SER-695; SER-1070 AND SER-1071. RX PubMed=3138233; DOI=10.1016/s0021-9258(18)37684-1; 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 [18] 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 verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [19] RP PROTEIN SEQUENCE OF 740-744 AND 746-747. RX PubMed=2985580; DOI=10.1016/s0021-9258(18)89002-0; RA Russo M.W., Lukas T.J., Cohen S., Staros J.V.; RT "Identification of residues in the nucleotide binding site of the epidermal RT growth factor receptor/kinase."; RL J. Biol. Chem. 260:5205-5208(1985). RN [20] 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 IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=16543144; DOI=10.1016/j.molcel.2006.02.018; RA Huang F., Kirkpatrick D., Jiang X., Gygi S.P., Sorkin A.; RT "Differential regulation of EGF receptor internalization and degradation by RT multiubiquitination within the kinase domain."; RL Mol. Cell 21:737-748(2006). RN [21] RP PARTIAL PROTEIN SEQUENCE, AND DISULFIDE BONDS. RX 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 [22] RP RECEPTOR ACTIVITY. RX PubMed=6325948; DOI=10.1038/309270a0; RA Mroczkowski B., Mosig G., Cohen S.; RT "ATP-stimulated interaction between epidermal growth factor receptor and RT supercoiled DNA."; RL Nature 309:270-273(1984). RN [23] RP REVIEW. RX PubMed=3039909; DOI=10.1146/annurev.bi.56.070187.004313; RA Carpenter G.; RT "Receptors for epidermal growth factor and other polypeptide mitogens."; RL Annu. Rev. Biochem. 56:881-914(1987). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, AND LIGAND-BINDING. RX 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 a RT domain required for ligand-induced internalization and calcium RT regulation."; RL Cell 59:33-43(1989). RN [25] RP PHOSPHORYLATION AT TYR-1110. RX PubMed=2543678; DOI=10.1016/s0021-9258(18)81674-x; RA Margolis B.L., Lax I., Kris R., Dombalagian M., Honegger A.M., Howk R., RA Givol D., Ullrich A., Schlessinger J.; RT "All autophosphorylation sites of epidermal growth factor (EGF) receptor RT and HER2/neu are located in their carboxyl-terminal tails. Identification RT of a novel site in EGF receptor."; RL J. Biol. Chem. 264:10667-10671(1989). RN [26] RP IDENTIFICATION OF AREG AS LIGAND, AND FUNCTION. RX PubMed=7679104; DOI=10.1016/s0021-9258(18)53862-x; RA Johnson G.R., Kannan B., Shoyab M., Stromberg K.; RT "Amphiregulin induces tyrosine phosphorylation of the epidermal growth RT factor receptor and p185erbB2. Evidence that amphiregulin acts exclusively RT through the epidermal growth factor receptor at the surface of human RT epithelial cells."; RL J. Biol. Chem. 268:2924-2931(1993). RN [27] RP INTERACTION WITH ZPR1. RX PubMed=8650580; DOI=10.1126/science.272.5269.1797; RA Galcheva-Gargova Z., Konstantinov K.N., Wu I.-H., Klier F.G., Barrett T., RA Davis R.J.; RT "Binding of zinc finger protein ZPR1 to the epidermal growth factor RT receptor."; RL Science 272:1797-1802(1996). RN [28] RP INTERACTION WITH ZPR1. RX PubMed=9852145; DOI=10.1083/jcb.143.6.1471; RA Gangwani L., Mikrut M., Galcheva-Gargova Z., Davis R.J.; RT "Interaction of ZPR1 with translation elongation factor-1alpha in RT proliferating cells."; RL J. Cell Biol. 143:1471-1484(1998). RN [29] RP PHOSPHORYLATION AT THR-678 AND THR-693. RX PubMed=10523301; DOI=10.1093/emboj/18.20.5567; RA Bagowski C.P., Stein-Gerlach M., Choidas A., Ullrich A.; RT "Cell-type specific phosphorylation of threonines T654 and T669 by PKD RT defines the signal capacity of the EGF receptor."; RL EMBO J. 18:5567-5576(1999). RN [30] RP IDENTIFICATION OF BETACELLULIN/BTC AS LIGAND. RX PubMed=8144591; DOI=10.1016/s0021-9258(17)36977-6; RA Watanabe T., Shintani A., Nakata M., Shing Y., Folkman J., Igarashi K., RA Sasada R.; RT "Recombinant human betacellulin. Molecular structure, biological RT activities, and receptor interaction."; RL J. Biol. Chem. 269:9966-9973(1994). RN [31] RP FUNCTION IN PHOSPHORYLATION OF CBL, AND 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 and RT association with epidermal growth factor (EGF) receptor upon EGF RT stimulation."; RL J. Biol. Chem. 270:20242-20245(1995). RN [32] RP GLYCOSYLATION AT ASN-128; ASN-175; ASN-413; ASN-444 AND ASN-528. RX PubMed=8962717; DOI=10.3109/08977199609034572; 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 the RT epidermal growth factor receptor expressed in Chinese hamster ovary RT fibroblasts."; RL Growth Factors 13:121-132(1996). RN [33] RP IDENTIFICATION OF EPIREGULIN/EREG AS LIGAND, AND FUNCTION. RX PubMed=9419975; DOI=10.1038/sj.onc.1201458; RA Komurasaki T., Toyoda H., Uchida D., Morimoto S.; RT "Epiregulin binds to epidermal growth factor receptor and ErbB-4 and RT induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB- RT 2, ErbB-3 and ErbB-4."; RL Oncogene 15:2841-2848(1997). RN [34] RP PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPN1 AND PTPN2. RX PubMed=9488479; DOI=10.1128/mcb.18.3.1622; RA Tiganis T., Bennett A.M., Ravichandran K.S., Tonks N.K.; RT "Epidermal growth factor receptor and the adaptor protein p52Shc are RT specific substrates of T-cell protein tyrosine phosphatase."; RL Mol. Cell. Biol. 18:1622-1634(1998). RN [35] RP INTERACTION WITH AP2M1. RX PubMed=10228163; DOI=10.1093/emboj/18.9.2489; RA Nesterov A., Carter R.E., Sorkina T., Gill G.N., Sorkin A.; RT "Inhibition of the receptor-binding function of clathrin adaptor protein RT AP-2 by dominant-negative mutant mu2 subunit and its effects on RT endocytosis."; RL EMBO J. 18:2489-2499(1999). RN [36] RP INTERACTION WITH GRB2; NCK1 AND NCK2. RX PubMed=10026169; DOI=10.1074/jbc.274.9.5542; RA Braverman L.E., Quilliam L.A.; RT "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing RT adapter protein having similar binding and biological properties to Nck."; RL J. Biol. Chem. 274:5542-5549(1999). RN [37] RP GLYCOSYLATION AT ASN-56; ASN-352; ASN-361; ASN-568 AND ASN-603. RX PubMed=10731668; DOI=10.1093/oxfordjournals.jbchem.a022585; RA Sato C., Kim J.-H., Abe Y., Saito K., Yokoyama S., Kohda D.; RT "Characterization of the N-oligosaccharides attached to the atypical Asn-X- RT Cys sequence of recombinant human epidermal growth factor receptor."; RL J. Biochem. 127:65-72(2000). RN [38] RP FUNCTION IN PHOSPHORYLATION OF RGS16. RX PubMed=11602604; DOI=10.1074/jbc.m108862200; RA Derrien A., Druey K.M.; RT "RGS16 function is regulated by epidermal growth factor receptor-mediated RT tyrosine phosphorylation."; RL J. Biol. Chem. 276:48532-48538(2001). RN [39] RP GLYCOSYLATION AT ASN-56; ASN-128; ASN-175; ASN-196; ASN-352; ASN-361; RP ASN-413; ASN-444; ASN-528; ASN-568; ASN-603 AND ASN-623. RX PubMed=12731890; DOI=10.1021/bi027101p; RA Zhen Y., Caprioli R.M., Staros J.V.; RT "Characterization of glycosylation sites of the epidermal growth factor RT receptor."; RL Biochemistry 42:5478-5492(2003). RN [40] RP FUNCTION IN CELL PROLIFERATION, INTERACTION WITH STAT3, AND PHOSPHORYLATION RP AT TYR-1092 AND TYR-1110. RX PubMed=12873986; RA Shao H., Cheng H.Y., Cook R.G., Tweardy D.J.; RT "Identification and characterization of signal transducer and activator of RT transcription 3 recruitment sites within the epidermal growth factor RT receptor."; RL Cancer Res. 63:3923-3930(2003). RN [41] RP ACTIVITY REGULATION, AND INTERACTION WITH LRIG1. RX PubMed=15282549; DOI=10.1038/sj.emboj.7600342; RA Gur G., Rubin C., Katz M., Amit I., Citri A., Nilsson J., Amariglio N., RA Henriksson R., Rechavi G., Hedman H., Wides R., Yarden Y.; RT "LRIG1 restricts growth factor signaling by enhancing receptor RT ubiquitylation and degradation."; RL EMBO J. 23:3270-3281(2004). RN [42] RP FUNCTION IN EGFR SIGNALING, IDENTIFICATION IN A COMPLEX WITH PIK3C2A AND RP ERBB2, IDENTIFICATION IN A COMPLEX WITH PIK3C2B AND ERBB2, INTERACTION WITH RP PIK3C2B, AND MUTAGENESIS OF TYR-1016; TYR-1092; TYR-1110; TYR-1172 AND RP 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 activated RT polypeptide growth factor receptors."; RL Mol. Cell. Biol. 20:3817-3830(2000). RN [43] RP FUNCTION IN NF-KAPPA-B ACTIVATION, AND INTERACTION WITH RIPK1. RX 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 protein RT and nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF- RT kappa B. Identification of a novel receptor-tyrosine kinase signalosome."; RL J. Biol. Chem. 276:8865-8874(2001). RN [44] RP FUNCTION IN PHOSPHORYLATION OF MUC1, AND INTERACTION WITH MUC1. RX PubMed=11483589; DOI=10.1074/jbc.c100359200; RA Li Y., Ren J., Yu W., Li Q., Kuwahara H., Yin L., Carraway K.L. III, RA Kufe D.; RT "The epidermal growth factor receptor regulates interaction of the human RT DF3/MUC1 carcinoma antigen with c-Src and beta-catenin."; RL J. Biol. Chem. 276:35239-35242(2001). RN [45] RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH SOCS5. RX PubMed=15590694; DOI=10.1074/jbc.m408575200; RA Kario E., Marmor M.D., Adamsky K., Citri A., Amit I., Amariglio N., RA Rechavi G., Yarden Y.; RT "Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor RT receptor signaling."; RL J. Biol. Chem. 280:7038-7048(2005). RN [46] RP IDENTIFICATION OF EPIGEN/EPGN AS A LIGAND, AND FUNCTION. RX PubMed=15611079; DOI=10.1074/jbc.m413919200; RA Kochupurakkal B.S., Harari D., Di-Segni A., Maik-Rachline G., Lyass L., RA Gur G., Kerber G., Citri A., Lavi S., Eilam R., Chalifa-Caspi V., RA Eshhar Z., Pikarsky E., Pinkas-Kramarski R., Bacus S.S., Yarden Y.; RT "Epigen, the last ligand of ErbB receptors, reveals intricate relationships RT between affinity and mitogenicity."; RL J. Biol. Chem. 280:8503-8512(2005). RN [47] 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 THR-693; RP SER-991 AND SER-1026, AND IDENTIFICATION BY 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 and RT epidermal growth factor receptor (EGFR)."; RL J. Proteome Res. 4:1155-1170(2005). RN [48] 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 in RT breast cancer cells."; RL Cancer Res. 65:7724-7732(2005). RN [49] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1172 AND TYR-1197, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [50] RP FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, RP INTERACTION WITH PCNA, AND SUBCELLULAR LOCATION. RX PubMed=17115032; DOI=10.1038/ncb1501; RA Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., RA McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.; RT "Tyrosine phosphorylation controls PCNA function through protein RT stability."; RL Nat. Cell Biol. 8:1359-1368(2006). RN [51] RP INTERACTION WITH STX19. RX PubMed=16420529; DOI=10.1111/j.1600-0854.2005.00378.x; RA Wang Y., Foo L.Y., Guo K., Gan B.Q., Zeng Q., Hong W., Tang B.L.; RT "Syntaxin 9 is enriched in skin hair follicle epithelium and interacts with RT the epidermal growth factor receptor."; RL Traffic 7:216-226(2006). RN [52] RP INTERACTION WITH PIKFYVE, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=17909029; DOI=10.1158/0008-5472.can-07-1333; RA Kim J., Jahng W.J., Di Vizio D., Lee J.S., Jhaveri R., Rubin M.A., RA Shisheva A., Freeman M.R.; RT "The phosphoinositide kinase PIKfyve mediates epidermal growth factor RT receptor trafficking to the nucleus."; RL Cancer Res. 67:9229-9237(2007). RN [53] RP TISSUE SPECIFICITY. RX PubMed=17671655; DOI=10.1172/jci31680; RA Groenestege W.M.T., Thebault S., van der Wijst J., van den Berg D., RA Janssen R., Tejpar S., van den Heuvel L.P., van Cutsem E., Hoenderop J.G., RA Knoers N.V., Bindels R.J.; RT "Impaired basolateral sorting of pro-EGF causes isolated recessive renal RT hypomagnesemia."; RL J. Clin. Invest. 117:2260-2267(2007). RN [54] RP INTERACTION WITH TNF2, AND SUBCELLULAR LOCATION. RX PubMed=17182860; DOI=10.1091/mbc.e06-02-0142; RA Shen F., Lin Q., Gu Y., Childress C., Yang W.; RT "Activated Cdc42-associated kinase 1 is a component of EGF receptor RT signaling complex and regulates EGF receptor degradation."; RL Mol. Biol. Cell 18:732-742(2007). RN [55] RP INTERACTION WITH NEU3, AND ACTIVITY REGULATION. RX PubMed=17334392; DOI=10.1038/sj.onc.1210341; RA Wada T., Hata K., Yamaguchi K., Shiozaki K., Koseki K., Moriya S., RA Miyagi T.; RT "A crucial role of plasma membrane-associated sialidase in the survival of RT human cancer cells."; RL Oncogene 26:2483-2490(2007). RN [56] RP INTERACTION WITH ATXN2. RX PubMed=18602463; DOI=10.1016/j.cellsig.2008.05.018; RA Nonis D., Schmidt M.H., van de Loo S., Eich F., Dikic I., Nowock J., RA Auburger G.; RT "Ataxin-2 associates with the endocytosis complex and affects EGF receptor RT trafficking."; RL Cell. Signal. 20:1725-1739(2008). RN [57] RP INTERACTION WITH GAB2. RX PubMed=19172738; DOI=10.1038/emboj.2008.159; RA Brummer T., Larance M., Herrera Abreu M.T., Lyons R.J., Timpson P., RA Emmerich C.H., Fleuren E.D.G., Lehrbach G.M., Schramek D., Guilhaus M., RA James D.E., Daly R.J.; RT "Phosphorylation-dependent binding of 14-3-3 terminates signalling by the RT Gab2 docking protein."; RL EMBO J. 27:2305-2316(2008). RN [58] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [59] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693; SER-695; SER-1064; RP SER-1081; SER-1166 AND TYR-1197, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [60] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-991; SER-995; TYR-998; RP SER-1039; THR-1041; SER-1042; SER-1064 AND SER-1166, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [61] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [62] RP ACTIVITY REGULATION BY PTPRJ AND PTPRK, PHOSPHORYLATION AT TYR-1197, RP DEPHOSPHORYLATION BY PTPRJ, SUBCELLULAR LOCATION, AND INTERACTION WITH CBL RP AND GRB2. RX PubMed=19836242; DOI=10.1016/j.cub.2009.09.048; RA Tarcic G., Boguslavsky S.K., Wakim J., Kiuchi T., Liu A., Reinitz F., RA Nathanson D., Takahashi T., Mischel P.S., Ng T., Yarden Y.; RT "An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase RT controlling EGFR endocytosis."; RL Curr. Biol. 19:1788-1798(2009). RN [63] RP INTERACTION WITH GAREM1. RX PubMed=19509291; DOI=10.1074/jbc.m109.021139; RA Tashiro K., Tsunematsu T., Okubo H., Ohta T., Sano E., Yamauchi E., RA Taniguchi H., Konishi H.; RT "GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, RT contributes to cellular transformation through the activation of RT extracellular signal-regulated kinase signaling."; RL J. Biol. Chem. 284:20206-20214(2009). RN [64] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-352; ASN-413 AND ASN-568. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [65] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [66] RP INTERACTION WITH GPER1. RX PubMed=19749156; DOI=10.1210/me.2009-0120; RA Vivacqua A., Lappano R., De Marco P., Sisci D., Aquila S., De Amicis F., RA Fuqua S.A., Ando S., Maggiolini M.; RT "G protein-coupled receptor 30 expression is up-regulated by EGF and TGF RT alpha in estrogen receptor alpha-positive cancer cells."; RL Mol. Endocrinol. 23:1815-1826(2009). RN [67] RP MUTAGENESIS OF 525-SER--ALA-1210; ASP-587; HIS-590 AND LYS-609. RX PubMed=19718021; DOI=10.1038/nature08297; RA Alvarado D., Klein D.E., Lemmon M.A.; RT "ErbB2 resembles an autoinhibited invertebrate epidermal growth factor RT receptor."; RL Nature 461:287-291(2009). RN [68] RP INTERACTION WITH COPG1, SUBCELLULAR LOCATION, AND TOPOLOGY. RX PubMed=20674546; DOI=10.1016/j.bbrc.2010.07.096; RA Wang Y.N., Wang H., Yamaguchi H., Lee H.J., Lee H.H., Hung M.C.; RT "COPI-mediated retrograde trafficking from the Golgi to the ER regulates RT EGFR nuclear transport."; RL Biochem. Biophys. Res. Commun. 399:498-504(2010). RN [69] RP INTERACTION WITH GPER1, AND SUBCELLULAR LOCATION. RX PubMed=20551055; DOI=10.1158/0008-5472.can-10-0408; RA Madeo A., Maggiolini M.; RT "Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol- RT induced gene expression and migration in breast cancer-associated RT fibroblasts."; RL Cancer Res. 70:6036-6046(2010). RN [70] RP FUNCTION, IDENTIFICATION IN COMPLEX WITH CCDC88A AND GNAI3, SUBCELLULAR RP LOCATION, AND PHOSPHORYLATION. RX PubMed=20462955; DOI=10.1091/mbc.e10-01-0028; RA Ghosh P., Beas A.O., Bornheimer S.J., Garcia-Marcos M., Forry E.P., RA Johannson C., Ear J., Jung B.H., Cabrera B., Carethers J.M., Farquhar M.G.; RT "A G{alpha}i-GIV molecular complex binds epidermal growth factor receptor RT and determines whether cells migrate or proliferate."; RL Mol. Biol. Cell 21:2338-2354(2010). RN [71] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693; SER-991; SER-1064 AND RP TYR-1197, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [72] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [73] RP PHOSPHORYLATION AT SER-229. RX PubMed=21487020; DOI=10.1074/jbc.m111.240796; RA Huang W.C., Chen Y.J., Li L.Y., Wei Y.L., Hsu S.C., Tsai S.L., Chiu P.C., RA Huang W.P., Wang Y.N., Chen C.H., Chang W.C., Chang W.C., Chen A.J., RA Tsai C.H., Hung M.C.; RT "Nuclear translocation of epidermal growth factor receptor by Akt-dependent RT phosphorylation enhances breast cancer-resistant protein expression in RT gefitinib-resistant cells."; RL J. Biol. Chem. 286:20558-20568(2011). RN [74] RP FUNCTION IN CELL PROLIFERATION AND CELL MIGRATION, METHYLATION AT ARG-1199 RP BY PRMT5, AND INTERACTION WITH PRMT5 AND PTPN6. RX PubMed=21258366; DOI=10.1038/ncb2158; RA Hsu J.M., Chen C.T., Chou C.K., Kuo H.P., Li L.Y., Lin C.Y., Lee H.J., RA Wang Y.N., Liu M., Liao H.W., Shi B., Lai C.C., Bedford M.T., Tsai C.H., RA Hung M.C.; RT "Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation RT negatively modulates EGFR-mediated ERK activation."; RL Nat. Cell Biol. 13:174-181(2011). RN [75] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=21516087; DOI=10.1038/nm.2341; RA Lupberger J., Zeisel M.B., Xiao F., Thumann C., Fofana I., Zona L., RA Davis C., Mee C.J., Turek M., Gorke S., Royer C., Fischer B., Zahid M.N., RA Lavillette D., Fresquet J., Cosset F.L., Rothenberg S.M., Pietschmann T., RA Patel A.H., Pessaux P., Doffoel M., Raffelsberger W., Poch O., RA McKeating J.A., Brino L., Baumert T.F.; RT "EGFR and EphA2 are host factors for hepatitis C virus entry and possible RT targets for antiviral therapy."; RL Nat. Med. 17:589-595(2011). RN [76] RP INTERACTION WITH FER, AND PHOSPHORYLATION. RX PubMed=21518868; DOI=10.1073/pnas.1105369108; RA Guo C., Stark G.R.; RT "FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine RT through EGF-dependent activation of NF-kappaB."; RL Proc. Natl. Acad. Sci. U.S.A. 108:7968-7973(2011). RN [77] RP INTERACTION WITH ANKRD13A; ANKRD13B AND ANKRD13D, UBIQUITINATION, AND RP SUBCELLULAR LOCATION. RX PubMed=22298428; DOI=10.1091/mbc.e11-09-0817; RA Tanno H., Yamaguchi T., Goto E., Ishido S., Komada M.; RT "The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor RT endocytosis from the plasma membrane."; RL Mol. Biol. Cell 23:1343-1353(2012). RN [78] RP UBIQUITINATION, AND DEUBIQUITINATION BY OTUD7B. RX PubMed=22179831; DOI=10.1038/onc.2011.587; RA Pareja F., Ferraro D.A., Rubin C., Cohen-Dvashi H., Zhang F., Aulmann S., RA Ben-Chetrit N., Pines G., Navon R., Crosetto N., Kostler W., Carvalho S., RA Lavi S., Schmitt F., Dikic I., Yakhini Z., Sinn P., Mills G.B., Yarden Y.; RT "Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression."; RL Oncogene 31:4599-4608(2012). RN [79] RP INTERACTION WITH CBL, AND PHOSPHORYLATION AT TYR-869; TYR-1016; TYR-1069; RP TYR-1092 AND TYR-1197. RX PubMed=23774213; DOI=10.1158/0008-5472.can-12-4441; RA Hong S.Y., Shih Y.P., Li T., Carraway K.L. III, Lo S.H.; RT "CTEN prolongs signaling by EGFR through reducing its ligand-induced RT degradation."; RL Cancer Res. 73:5266-5276(2013). RN [80] RP INTERACTION WITH RNF115 AND RNF126. RX PubMed=23418353; DOI=10.1242/jcs.116129; RA Smith C.J., Berry D.M., McGlade C.J.; RT "The E3 ubiquitin ligases RNF126 and Rabring7 regulate endosomal sorting of RT the epidermal growth factor receptor."; RL J. Cell Sci. 126:1366-1380(2013). RN [81] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693 AND SER-1064, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [82] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693; SER-991; SER-1026 AND RP SER-1166, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [83] RP INTERACTION WITH CCDC88A AND GNAI3. RX PubMed=25187647; DOI=10.1091/mbc.e14-05-0978; RA Lin C., Ear J., Midde K., Lopez-Sanchez I., Aznar N., Garcia-Marcos M., RA Kufareva I., Abagyan R., Ghosh P.; RT "Structural basis for activation of trimeric Gi proteins by multiple growth RT factor receptors via GIV/Girdin."; RL Mol. Biol. Cell 25:3654-3671(2014). RN [84] RP SUBCELLULAR LOCATION, AND INTERACTION WITH CD44. RX PubMed=23589287; DOI=10.1074/jbc.m113.451336; RA Midgley A.C., Rogers M., Hallett M.B., Clayton A., Bowen T., Phillips A.O., RA Steadman R.; RT "Transforming growth factor-beta1 (TGF-beta1)-stimulated fibroblast to RT myofibroblast differentiation is mediated by hyaluronan (HA)-facilitated RT epidermal growth factor receptor (EGFR) and CD44 co-localization in lipid RT rafts."; RL J. Biol. Chem. 288:14824-14838(2013). RN [85] RP INTERACTION WITH GPRC5A. RX PubMed=25311788; DOI=10.1186/1476-4598-13-233; RA Lin X., Zhong S., Ye X., Liao Y., Yao F., Yang X., Sun B., Zhang J., Li Q., RA Gao Y., Wang Y., Liu J., Han B., Chin Y.E., Zhou B.P., Deng J.; RT "EGFR phosphorylates and inhibits lung tumor suppressor GPRC5A in lung RT cancer."; RL Mol. Cancer 13:233-233(2014). RN [86] RP INTERACTION WITH FAM83B. RX PubMed=23912460; DOI=10.1038/onc.2013.293; RA Cipriano R., Bryson B.L., Miskimen K.L., Bartel C.A., Hernandez-Sanchez W., RA Bruntz R.C., Scott S.A., Lindsley C.W., Brown H.A., Jackson M.W.; RT "Hyperactivation of EGFR and downstream effector phospholipase D1 by RT oncogenic FAM83B."; RL Oncogene 33:3298-3306(2014). RN [87] RP GLYCOSYLATION AT ASN-528, AND ACTIVITY REGULATION. RX PubMed=25922362; DOI=10.1093/glycob/cwv026; RA Mozzi A., Forcella M., Riva A., Difrancesco C., Molinari F., Martin V., RA Papini N., Bernasconi B., Nonnis S., Tedeschi G., Mazzucchelli L., RA Monti E., Fusi P., Frattini M.; RT "NEU3 activity enhances EGFR activation without affecting EGFR expression RT and acts on its sialylation levels."; RL Glycobiology 25:855-868(2015). RN [88] RP FUNCTION, PALMITOYLATION AT CYS-1049 AND CYS-1146, IDENTIFICATION BY MASS RP SPECTROMETRY, UBIQUITINATION, PHOSPHORYLATION AT TYR-1092; TYR-1172 AND RP TYR-1197, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 1048-ALA--ALA-1210; RP CYS-1049 AND CYS-1146. RX PubMed=27153536; DOI=10.1016/j.molcel.2016.04.003; RA Runkle K.B., Kharbanda A., Stypulkowski E., Cao X.J., Wang W., Garcia B.A., RA Witze E.S.; RT "Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on RT EGFR Signaling."; RL Mol. Cell 62:385-396(2016). RN [89] RP INTERACTION WITH PGRMC1. RX PubMed=26988023; DOI=10.1038/ncomms11030; RA Kabe Y., Nakane T., Koike I., Yamamoto T., Sugiura Y., Harada E., RA Sugase K., Shimamura T., Ohmura M., Muraoka K., Yamamoto A., Uchida T., RA Iwata S., Yamaguchi Y., Krayukhina E., Noda M., Handa H., Ishimori K., RA Uchiyama S., Kobayashi T., Suematsu M.; RT "Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer RT proliferation and chemoresistance."; RL Nat. Commun. 7:11030-11030(2016). RN [90] RP INTERACTION WITH LAPTM4B. RX PubMed=28479384; DOI=10.1016/j.gene.2017.05.006; RA Tian M., Chen Y., Tian D., Qiao X., Ma Z., Li J.; RT "Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer RT cells."; RL Gene 626:48-53(2017). RN [91] RP HYDROXYBUTYRYLATION AT LYS-745. RX PubMed=29192674; DOI=10.1038/cr.2017.149; RA Huang H., Luo Z., Qi S., Huang J., Xu P., Wang X., Gao L., Li F., Wang J., RA Zhao W., Gu W., Chen Z., Dai L., Dai J., Zhao Y.; RT "Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation RT pathway."; RL Cell Res. 28:111-125(2018). RN [92] RP INTERACTION WITH TRAF4. RX PubMed=30352854; DOI=10.1073/pnas.1809599115; RA Cai G., Zhu L., Chen X., Sun K., Liu C., Sen G.C., Stark G.R., Qin J., RA Li X.; RT "TRAF4 binds to the juxtamembrane region of EGFR directly and promotes RT kinase activation."; RL Proc. Natl. Acad. Sci. U.S.A. 115:11531-11536(2018). RN [93] RP UBIQUITINATION BY ZNRF1 AND CBL. RX PubMed=33996800; DOI=10.3389/fcell.2021.642625; RA Shen C.H., Chou C.C., Lai T.Y., Hsu J.E., Lin Y.S., Liu H.Y., Chen Y.K., RA Ho I.L., Hsu P.H., Chuang T.H., Lee C.Y., Hsu L.C.; RT "ZNRF1 Mediates Epidermal Growth Factor Receptor Ubiquitination to Control RT Receptor Lysosomal Trafficking and Degradation."; RL Front. Cell Dev. Biol. 9:642625-642625(2021). RN [94] {ECO:0007744|PDB:1MOX} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 25-525 IN COMPLEX WITH TGFA, RP FUNCTION, GLYCOSYLATION AT ASN-56; ASN-196 AND ASN-352, AND DISULFIDE RP BONDS. RX PubMed=12297049; DOI=10.1016/s0092-8674(02)00940-6; RA Garrett T.P., McKern N.M., Lou M., Elleman T.C., Adams T.E., Lovrecz G.O., RA Zhu H.J., Walker F., Frenkel M.J., Hoyne P.A., Jorissen R.N., Nice E.C., RA Burgess A.W., Ward C.W.; RT "Crystal structure of a truncated epidermal growth factor receptor RT extracellular domain bound to transforming growth factor alpha."; RL Cell 110:763-773(2002). RN [95] {ECO:0007744|PDB:1IVO} RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 25-646 IN COMPLEX WITH EGF, RP FUNCTION IN MAPK1 AND/OR MAPK3 ACTIVATION, SUBUNIT, SUBCELLULAR LOCATION, RP MUTAGENESIS OF TYR-275; PHE-287; ARG-309 AND ARG-429, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-56; ASN-175; ASN-196; ASN-352; ASN-361 AND ASN-444. RX PubMed=12297050; DOI=10.1016/s0092-8674(02)00963-7; RA Ogiso H., Ishitani R., Nureki O., Fukai S., Yamanaka M., Kim J.H., RA Saito K., Sakamoto A., Inoue M., Shirouzu M., Yokoyama S.; RT "Crystal structure of the complex of human epidermal growth factor and RT receptor extracellular domains."; RL Cell 110:775-787(2002). RN [96] {ECO:0007744|PDB:1NQL} RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 25-642 IN COMPLEX WITH EGF, RP FUNCTION, SUBUNIT, MUTAGENESIS OF 587-ASP--HIS-590 AND LYS-609, DISULFIDE RP BONDS, AND GLYCOSYLATION AT ASN-352; ASN-361; ASN-444; ASN-528; ASN-568 AND RP ASN-603. RX PubMed=12620237; DOI=10.1016/s1097-2765(03)00047-9; RA Ferguson K.M., Berger M.B., Mendrola J.M., Cho H.S., Leahy D.J., RA Lemmon M.A.; RT "EGF activates its receptor by removing interactions that autoinhibit RT ectodomain dimerization."; RL Mol. Cell 11:507-517(2003). RN [97] {ECO:0007744|PDB:1XKK} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 695-1022 IN COMPLEX WITH RP GW572016, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=15374980; DOI=10.1158/0008-5472.can-04-1168; RA Wood E.R., Truesdale A.T., McDonald O.B., Yuan D., Hassell A., RA Dickerson S.H., Ellis B., Pennisi C., Horne E., Lackey K., Alligood K.J., RA Rusnak D.W., Gilmer T.M., Shewchuk L.; RT "A unique structure for epidermal growth factor receptor bound to GW572016 RT (Lapatinib): relationships among protein conformation, inhibitor off-rate, RT and receptor activity in tumor cells."; RL Cancer Res. 64:6652-6659(2004). RN [98] {ECO:0007744|PDB:1YY9} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 25-642 IN COMPLEX WITH CETUXIMAB. RX PubMed=15837620; DOI=10.1016/j.ccr.2005.03.003; RA Li S., Schmitz K.R., Jeffrey P.D., Wiltzius J.J., Kussie P., Ferguson K.M.; RT "Structural basis for inhibition of the epidermal growth factor receptor by RT cetuximab."; RL Cancer Cell 7:301-311(2005). RN [99] RP STRUCTURE BY NMR OF 669-721. RX PubMed=15840573; DOI=10.1074/jbc.m502698200; RA Choowongkomon K., Carlin C.R., Sonnichsen F.D.; RT "A structural model for the membrane-bound form of the juxtamembrane domain RT of the epidermal growth factor receptor."; RL J. Biol. Chem. 280:24043-24052(2005). RN [100] {ECO:0007744|PDB:2ITN, ECO:0007744|PDB:2ITO, ECO:0007744|PDB:2ITP, ECO:0007744|PDB:2ITQ, ECO:0007744|PDB:2ITT, ECO:0007744|PDB:2ITU, ECO:0007744|PDB:2ITV, ECO:0007744|PDB:2J6M} RP X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) OF 696-1022 OF WILD-TYPE AND RP VARIANTS SER-719 AND ARG-858 IN COMPLEXES WITH ATP ANALOGS AND SYNTHETIC RP INHIBITORS, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND CHARACTERIZATION RP OF VARIANTS SER-719 AND ARG-858. RX PubMed=17349580; DOI=10.1016/j.ccr.2006.12.017; RA Yun C.H., Boggon T.J., Li Y., Woo M.S., Greulich H., Meyerson M., Eck M.J.; RT "Structures of lung cancer-derived EGFR mutants and inhibitor complexes: RT mechanism of activation and insights into differential inhibitor RT sensitivity."; RL Cancer Cell 11:217-227(2007). RN [101] RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 702-1022 IN COMPLEX WITH ERRFI1, RP ACTIVITY REGULATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, AND RP INTERACTION WITH ERRFI1. RX PubMed=18046415; DOI=10.1038/nature05998; RA Zhang X., Pickin K.A., Bose R., Jura N., Cole P.A., Kuriyan J.; RT "Inhibition of the EGF receptor by binding of MIG6 to an activating kinase RT domain interface."; RL Nature 450:741-744(2007). RN [102] {ECO:0007744|PDB:2JIT, ECO:0007744|PDB:2JIU, ECO:0007744|PDB:2JIV} RP X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 695-1022 OF VARIANT MET-790, RP CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANT MET-790. RX PubMed=18227510; DOI=10.1073/pnas.0709662105; RA Yun C.H., Mengwasser K.E., Toms A.V., Woo M.S., Greulich H., Wong K.K., RA Meyerson M., Eck M.J.; RT "The T790M mutation in EGFR kinase causes drug resistance by increasing the RT affinity for ATP."; RL Proc. Natl. Acad. Sci. U.S.A. 105:2070-2075(2008). RN [103] {ECO:0007744|PDB:3GT8} RP X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF 696-1022, CATALYTIC ACTIVITY, RP PHOSPHORYLATION AT TYR-998; TYR-1016 AND TYR-1197, MUTAGENESIS OF LEU-688; RP GLU-690; LEU-692; ARG-977 AND 1005-GLU-ASP-1006, AND SUBUNIT. RX PubMed=19563760; DOI=10.1016/j.cell.2009.04.025; RA Jura N., Endres N.F., Engel K., Deindl S., Das R., Lamers M.H., RA Wemmer D.E., Zhang X., Kuriyan J.; RT "Mechanism for activation of the EGF receptor catalytic domain by the RT juxtamembrane segment."; RL Cell 137:1293-1307(2009). RN [104] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 669-1022 OF MUTANT MET-745, RP CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, RP AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LEU-688; VAL-689; GLU-690; LEU-692; RP THR-693; PRO-694; PRO-699; ASN-700; LEU-704; ARG-705; ILE-706 AND LYS-745. RX PubMed=19560417; DOI=10.1016/j.molcel.2009.04.034; RA Red Brewer M., Choi S.H., Alvarado D., Moravcevic K., Pozzi A., RA Lemmon M.A., Carpenter G.; RT "The juxtamembrane region of the EGF receptor functions as an activation RT domain."; RL Mol. Cell 34:641-651(2009). RN [105] RP STRUCTURE BY NMR OF 634-677 IN COMPLEX WITH ERBB2, AND SUBUNIT. RX PubMed=20471394; DOI=10.1016/j.jmb.2010.05.016; RA Mineev K.S., Bocharov E.V., Pustovalova Y.E., Bocharova O.V., Chupin V.V., RA Arseniev A.S.; RT "Spatial structure of the transmembrane domain heterodimer of ErbB1 and RT ErbB2 receptor tyrosine kinases."; RL J. Mol. Biol. 400:231-243(2010). RN [106] {ECO:0007744|PDB:3NJP} RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 25-638 IN COMPLEX WITH EGF, RP FUNCTION, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-56; ASN-73; RP ASN-175; ASN-196; ASN-352; ASN-361; ASN-444 AND ASN-528. RX PubMed=20837704; DOI=10.1128/mcb.00742-10; RA Lu C., Mi L.Z., Grey M.J., Zhu J., Graef E., Yokoyama S., Springer T.A.; RT "Structural evidence for loose linkage between ligand binding and kinase RT activation in the epidermal growth factor receptor."; RL Mol. Cell. Biol. 30:5432-5443(2010). RN [107] RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 1066-1076 IN COMPLEX WITH CBLB, RP AND INTERACTION WITH CBLB. RG Structural genomics consortium; RT "Crystal structure of Cbl-b TKB domain in complex with EGFR pY1069 RT peptide."; RL Submitted (OCT-2010) to the PDB data bank. RN [108] RP X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 1062-1074 IN COMPLEX WITH CBLC, RP PHOSPHORYLATION AT TYR-1069, INTERACTION WITH CBLC, AND MUTAGENESIS OF RP GLN-1067; ARG-1068 AND TYR-1069. RX PubMed=22888118; DOI=10.1093/jb/mvs085; RA Takeshita K., Tezuka T., Isozaki Y., Yamashita E., Suzuki M., Kim M., RA Yamanashi Y., Yamamoto T., Nakagawa A.; RT "Structural flexibility regulates phosphopeptide-binding activity of the RT tyrosine kinase binding domain of Cbl-c."; RL J. Biochem. 152:487-495(2012). RN [109] RP VARIANTS ALA-709; GLY-709; CYS-719; SER-719; 746-GLU--ALA-750 DEL; RP 746-GLU--THR-751 DELINS ALA; 746-GLU--SER-752 DELINS ASP; 747-LEU--THR-751 RP DEL; ILE-768; MET-769; VAL-833; LEU-835; VAL-838; ARG-858 AND GLN-861. RX PubMed=15623594; DOI=10.1158/1078-0432.ccr-04-1245; RA Huang S.F., Liu H.P., Li L.H., Ku Y.C., Fu Y.N., Tsai H.Y., Chen Y.T., RA Lin Y.F., Chang W.C., Kuo H.P., Wu Y.C., Chen Y.R., Tsai S.F.; RT "High frequency of epidermal growth factor receptor mutations with complex RT patterns in non-small cell lung cancers related to gefitinib responsiveness RT in Taiwan."; RL Clin. Cancer Res. 10:8195-8203(2004). RN [110] RP VARIANTS SER-719 AND ARG-858, AND POSSIBLE INVOLVEMENT IN LUNG CANCER. 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 [111] RP VARIANTS ALA-709; LYS-709; ALA-719; ASP-719; CYS-719; SER-719; SER-724; RP LYS-734; GLU-746 DEL; PHE-747; 747-LEU--GLU-749 DEL; PRO-748; RP 752-SER--ILE-759 DEL; ARG-787; MET-790; VAL-833; LEU-834; MET-858; ARG-858; RP GLN-861 AND GLU-873, AND POSSIBLE INVOLVEMENT IN LUNG CANCER. 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., Lam W.K., RA Chiu S.W., Girard L., Minna J.D., Gazdar A.F., Wong M.P.; RT "Distinct epidermal growth factor receptor and KRAS mutation patterns in RT non-small cell lung cancer patients with different tobacco exposure and RT clinicopathologic features."; RL Clin. Cancer Res. 12:1647-1653(2006). RN [112] RP CHARACTERIZATION OF VARIANTS ALA-709; GLY-709; SER-719; ILE-768; VAL-833; RP LEU-835; VAL-838; ARG-858 AND GLN-861. RX PubMed=16205628; DOI=10.1038/sj.onc.1209159; RA Chen Y.R., Fu Y.N., Lin C.H., Yang S.T., Hu S.F., Chen Y.T., Tsai S.F., RA Huang S.F.; RT "Distinctive activation patterns in constitutively active and gefitinib- RT sensitive EGFR mutants."; RL Oncogene 25:1205-1215(2006). RN [113] RP VARIANT 30-VAL--ARG-297 DEL, AND POSSIBLE INVOLVEMENT IN LUNG CANCER. RX PubMed=16672372; DOI=10.1073/pnas.0510284103; RA Ji H., Zhao X., Yuza Y., Shimamura T., Li D., Protopopov A., Jung B.L., RA McNamara K., Xia H., Glatt K.A., Thomas R.K., Sasaki H., Horner J.W., RA Eck M., Mitchell A., Sun Y., Al-Hashem R., Bronson R.T., Rabindran S.K., RA Discafani C.M., Maher E., Shapiro G.I., Meyerson M., Wong K.K.; RT "Epidermal growth factor receptor variant III mutations in lung RT tumorigenesis and sensitivity to tyrosine kinase inhibitors."; RL Proc. Natl. Acad. Sci. U.S.A. 103:7817-7822(2006). RN [114] RP VARIANTS [LARGE SCALE ANALYSIS] LYS-521; ARG-1034 AND VAL-1210. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [115] RP VARIANT NISBD2 ASP-428, CHARACTERIZATION OF VARIANT NISBD2 ASP-428, AND RP INVOLVEMENT IN NISBD2. RX PubMed=24691054; DOI=10.1038/jid.2014.164; RA Campbell P., Morton P.E., Takeichi T., Salam A., Roberts N., RA Proudfoot L.E., Mellerio J.E., Aminu K., Wellington C., Patil S.N., RA Akiyama M., Liu L., McMillan J.R., Aristodemou S., Ishida-Yamamoto A., RA Abdul-Wahab A., Petrof G., Fong K., Harnchoowong S., Stone K.L., RA Harper J.I., McLean W.H., Simpson M.A., Parsons M., McGrath J.A.; RT "Epithelial inflammation resulting from an inherited loss-of-function RT mutation in EGFR."; RL J. Invest. Dermatol. 134:2570-2578(2014). CC -!- FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family CC and activating several signaling cascades to convert extracellular cues CC into appropriate cellular responses (PubMed:2790960, PubMed:10805725, CC PubMed:27153536). Known ligands include EGF, TGFA/TGF-alpha, AREG, CC epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin- CC binding EGF (PubMed:2790960, PubMed:7679104, PubMed:8144591, CC PubMed:9419975, PubMed:15611079, PubMed:12297049, PubMed:27153536, CC PubMed:20837704, PubMed:17909029). Ligand binding triggers receptor CC homo- and/or heterodimerization and autophosphorylation on key CC cytoplasmic residues. The phosphorylated receptor recruits adapter CC proteins like GRB2 which in turn activates complex downstream signaling CC cascades. Activates at least 4 major downstream signaling cascades CC including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs CC modules (PubMed:27153536). May also activate the NF-kappa-B signaling CC cascade (PubMed:11116146). Also directly phosphorylates other proteins CC like RGS16, activating its GTPase activity and probably coupling the CC EGF receptor signaling to the G protein-coupled receptor signaling CC (PubMed:11602604). Also phosphorylates MUC1 and increases its CC interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). CC Positively regulates cell migration via interaction with CCDC88A/GIV CC which retains EGFR at the cell membrane following ligand stimulation, CC promoting EGFR signaling which triggers cell migration CC (PubMed:20462955). Plays a role in enhancing learning and memory CC performance (By similarity). Plays a role in mammalian pain signaling CC (long-lasting hypersensitivity) (By similarity). CC {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, CC ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, CC ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, CC ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, CC ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, CC ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, CC ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, CC ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, CC ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, CC ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, CC ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, CC ECO:0000269|PubMed:9419975}. CC -!- FUNCTION: Isoform 2 may act as an antagonist of EGF action. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C CC virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV CC entry by promoting the formation of the CD81-CLDN1 receptor complexes CC that are essential for HCV entry and by enhancing membrane fusion of CC cells expressing HCV envelope glycoproteins. CC {ECO:0000269|PubMed:21516087}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:17349580, CC ECO:0000269|PubMed:18046415, ECO:0000269|PubMed:18227510, CC ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:19563760}; CC -!- ACTIVITY REGULATION: Endocytosis and inhibition of the activated EGFR CC by phosphatases like PTPRJ and PTPRK constitute immediate regulatory CC mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR CC endocytosis and activity. Moreover, inducible feedback inhibitors CC including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative CC regulatory mechanisms for the EGFR signaling. Up-regulated by NEU3- CC mediated desialylation of N-linked glycan at Asn-528. CC {ECO:0000269|PubMed:15282549, ECO:0000269|PubMed:15590694, CC ECO:0000269|PubMed:17334392, ECO:0000269|PubMed:18046415, CC ECO:0000269|PubMed:19836242, ECO:0000269|PubMed:25922362}. CC -!- SUBUNIT: Binding of the ligand triggers homo- and/or heterodimerization CC of the receptor triggering its autophosphorylation. Heterodimer with CC ERBB2 (PubMed:10805725). Forms a complex with CCDC88A/GIV (via SH2-like CC regions) and GNAI3 which leads to enhanced EGFR signaling and CC triggering of cell migration; binding to CCDC88A requires CC autophosphorylation of the EGFR C-terminal region, and ligand CC stimulation is required for recruitment of GNAI3 to the complex CC (PubMed:20462955, PubMed:25187647). Interacts with ERRFI1; inhibits CC dimerization of the kinase domain and autophosphorylation CC (PubMed:18046415). Part of a complex with ERBB2 and either PIK3C2A or CC PIK3C2B (PubMed:10805725). Interacts with GRB2; an adapter protein CC coupling the receptor to downstream signaling pathways. Interacts with CC GAB2; involved in signaling downstream of EGFR. Interacts with STAT3; CC mediates EGFR downstream signaling in cell proliferation. Interacts CC with RIPK1; involved in NF-kappa-B activation. Interacts CC (autophosphorylated) with CBL, CBLB and CBLC; involved in EGFR CC ubiquitination and regulation; interaction with CBL is reduced in the CC presence of tensin TNS4 (PubMed:23774213). Interacts with SOCS5; CC regulates EGFR degradation through ELOC- and ELOB-mediated CC ubiquitination and proteasomal degradation. Interacts with PRMT5; CC methylates EGFR and enhances interaction with PTPN6. Interacts CC (phosphorylated) with PTPN6; inhibits EGFR-dependent activation of CC MAPK/ERK. Interacts with COPG1; essential for regulation of EGF- CC dependent nuclear transport of EGFR by retrograde trafficking from the CC Golgi to the ER. Interacts with TNK2; this interaction is dependent on CC EGF stimulation and kinase activity of EGFR. Interacts with PCNA; CC positively regulates PCNA (PubMed:17115032). Interacts with PELP1. CC Interacts with MUC1. Interacts with AP2M1. Interacts with FER. May CC interact with EPS8; mediates EPS8 phosphorylation. Interacts (via SH2 CC domains) with GRB2, NCK1 and NCK2 (PubMed:10026169). Interacts with CC ATXN2. Interacts with GAREM1. Interacts (ubiquitinated) with CC ANKRD13A/B/D; the interaction is direct and may regulate EGFR CC internalization after EGF stimulation. Interacts with GPER1; the CC interaction occurs in an estrogen-dependent manner. Interacts (via C- CC terminal cytoplasmic kinase domain) with ZPR1 (via zinc fingers). CC Interacts with RNF115 and RNF126 (PubMed:23418353). Interacts with CC GPRC5A (via its transmembrane domain) (PubMed:25311788). Interacts with CC FAM83B; positively regulates EGFR inducing its autophosphorylation in CC absence of stimulation by EGF (PubMed:23912460). Interacts with CC LAPTM4B; positively correlates with EGFR activation (PubMed:28479384). CC Interacts with STX19 (PubMed:16420529). Interacts with CD44 CC (PubMed:23589287). Interacts with PGRMC1; the interaction requires CC PGRMC1 homodimerization (PubMed:26988023). Interacts with PIKFYVE CC (PubMed:17909029). Interacts with NEU3. Interacts with TRAF4 CC (PubMed:30352854). Interacts with the ant venom OMEGA- CC myrmeciitoxin(02)-Mg1a (By similarity). {ECO:0000250|UniProtKB:Q01279, CC ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:10228163, CC ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, CC ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:12297050, CC ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, CC ECO:0000269|PubMed:15282549, ECO:0000269|PubMed:15374980, CC ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15837620, CC ECO:0000269|PubMed:16140940, ECO:0000269|PubMed:16420529, CC ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17182860, CC ECO:0000269|PubMed:17334392, ECO:0000269|PubMed:17909029, CC ECO:0000269|PubMed:18046415, ECO:0000269|PubMed:18602463, CC ECO:0000269|PubMed:19172738, ECO:0000269|PubMed:19509291, CC ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:19563760, CC ECO:0000269|PubMed:19749156, ECO:0000269|PubMed:19836242, CC ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20471394, CC ECO:0000269|PubMed:20551055, ECO:0000269|PubMed:20674546, CC ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, CC ECO:0000269|PubMed:21518868, ECO:0000269|PubMed:22298428, CC ECO:0000269|PubMed:22888118, ECO:0000269|PubMed:23418353, CC ECO:0000269|PubMed:23589287, ECO:0000269|PubMed:23774213, CC ECO:0000269|PubMed:23912460, ECO:0000269|PubMed:25187647, CC ECO:0000269|PubMed:25311788, ECO:0000269|PubMed:26988023, CC ECO:0000269|PubMed:28479384, ECO:0000269|PubMed:7657591, CC ECO:0000269|PubMed:8650580, ECO:0000269|PubMed:9852145, CC ECO:0000269|Ref.107}. CC -!- INTERACTION: CC P00533; P00519: ABL1; NbExp=3; IntAct=EBI-297353, EBI-375543; CC P00533; P42684: ABL2; NbExp=9; IntAct=EBI-297353, EBI-1102694; CC P00533; Q15109: AGER; NbExp=2; IntAct=EBI-297353, EBI-1646426; CC P00533; Q9UKV8: AGO2; NbExp=11; IntAct=EBI-297353, EBI-528269; CC P00533; Q09666: AHNAK; NbExp=4; IntAct=EBI-297353, EBI-2555881; CC P00533; O00170: AIP; NbExp=2; IntAct=EBI-297353, EBI-704197; CC P00533; Q02952: AKAP12; NbExp=3; IntAct=EBI-297353, EBI-2562430; CC P00533; P49418: AMPH; NbExp=2; IntAct=EBI-297353, EBI-7121510; CC P00533; Q92625: ANKS1A; NbExp=7; IntAct=EBI-297353, EBI-1048612; CC P00533; P04083: ANXA1; NbExp=3; IntAct=EBI-297353, EBI-354007; CC P00533; P07355: ANXA2; NbExp=4; IntAct=EBI-297353, EBI-352622; CC P00533; Q10567: AP1B1; NbExp=4; IntAct=EBI-297353, EBI-1171303; CC P00533; Q96CW1: AP2M1; NbExp=8; IntAct=EBI-297353, EBI-297683; CC P00533; O00213: APBB1; NbExp=4; IntAct=EBI-297353, EBI-81694; CC P00533; Q92870: APBB2; NbExp=7; IntAct=EBI-297353, EBI-79277; CC P00533; O95704: APBB3; NbExp=2; IntAct=EBI-297353, EBI-286427; CC P00533; Q9UKG1: APPL1; NbExp=3; IntAct=EBI-297353, EBI-741243; CC P00533; O14965: AURKA; NbExp=4; IntAct=EBI-297353, EBI-448680; CC P00533; P30530: AXL; NbExp=4; IntAct=EBI-297353, EBI-2850927; CC P00533; Q9UQB8: BAIAP2; NbExp=4; IntAct=EBI-297353, EBI-525456; CC P00533; Q9BXH1: BBC3; NbExp=10; IntAct=EBI-297353, EBI-519884; CC P00533; Q14457: BECN1; NbExp=7; IntAct=EBI-297353, EBI-949378; CC P00533; P51451: BLK; NbExp=3; IntAct=EBI-297353, EBI-2105445; CC P00533; P62158: CALM3; NbExp=6; IntAct=EBI-297353, EBI-397435; CC P00533; P49069: CAMLG; NbExp=3; IntAct=EBI-297353, EBI-1748958; CC P00533; Q03135: CAV1; NbExp=7; IntAct=EBI-297353, EBI-603614; CC P00533; P51636: CAV2; NbExp=3; IntAct=EBI-297353, EBI-603607; CC P00533; P22681: CBL; NbExp=22; IntAct=EBI-297353, EBI-518228; CC P00533; Q16543: CDC37; NbExp=13; IntAct=EBI-297353, EBI-295634; CC P00533; P12830: CDH1; NbExp=4; IntAct=EBI-297353, EBI-727477; CC P00533; P06493: CDK1; NbExp=3; IntAct=EBI-297353, EBI-444308; CC P00533; P23528: CFL1; NbExp=3; IntAct=EBI-297353, EBI-352733; CC P00533; Q9BZP6: CHIA; NbExp=2; IntAct=EBI-297353, EBI-14357960; CC P00533; Q9NSE2: CISH; NbExp=4; IntAct=EBI-297353, EBI-617866; CC P00533; Q7Z7G1: CLNK; NbExp=2; IntAct=EBI-297353, EBI-7878194; CC P00533; Q8WXI2: CNKSR2; NbExp=2; IntAct=EBI-297353, EBI-1045119; CC P00533; P46108: CRK; NbExp=4; IntAct=EBI-297353, EBI-886; CC P00533; P46108-1: CRK; NbExp=3; IntAct=EBI-297353, EBI-287556; CC P00533; P46109: CRKL; NbExp=4; IntAct=EBI-297353, EBI-910; CC P00533; O60716: CTNND1; NbExp=5; IntAct=EBI-297353, EBI-701927; CC P00533; Q14247: CTTN; NbExp=4; IntAct=EBI-297353, EBI-351886; CC P00533; Q7L591: DOK3; NbExp=2; IntAct=EBI-297353, EBI-2834978; CC P00533; Q6PKX4: DOK6; NbExp=2; IntAct=EBI-297353, EBI-2880244; CC P00533; P01133: EGF; NbExp=29; IntAct=EBI-297353, EBI-640857; CC P00533; P00533: EGFR; NbExp=29; IntAct=EBI-297353, EBI-297353; CC P00533; Q6UW88: EPGN; NbExp=3; IntAct=EBI-297353, EBI-15482510; CC P00533; Q12929: EPS8; NbExp=4; IntAct=EBI-297353, EBI-375576; CC P00533; P04626: ERBB2; NbExp=25; IntAct=EBI-297353, EBI-641062; CC P00533; P21860: ERBB3; NbExp=14; IntAct=EBI-297353, EBI-720706; CC P00533; Q15303: ERBB4; NbExp=3; IntAct=EBI-297353, EBI-80371; CC P00533; P07992: ERCC1; NbExp=21; IntAct=EBI-297353, EBI-750962; CC P00533; O14944: EREG; NbExp=3; IntAct=EBI-297353, EBI-17272224; CC P00533; Q9UJM3: ERRFI1; NbExp=15; IntAct=EBI-297353, EBI-2941912; CC P00533; P03372: ESR1; NbExp=2; IntAct=EBI-297353, EBI-78473; CC P00533; P03372-4: ESR1; NbExp=4; IntAct=EBI-297353, EBI-4309277; CC P00533; Q92731: ESR2; NbExp=8; IntAct=EBI-297353, EBI-78505; CC P00533; Q96A65: EXOC4; NbExp=2; IntAct=EBI-297353, EBI-355383; CC P00533; P15311: EZR; NbExp=3; IntAct=EBI-297353, EBI-1056902; CC P00533; Q9BXW9: FANCD2; NbExp=2; IntAct=EBI-297353, EBI-359343; CC P00533; P09769: FGR; NbExp=3; IntAct=EBI-297353, EBI-1383732; CC P00533; Q13451: FKBP5; NbExp=2; IntAct=EBI-297353, EBI-306914; CC P00533; Q14318: FKBP8; NbExp=4; IntAct=EBI-297353, EBI-724839; CC P00533; Q13480: GAB1; NbExp=5; IntAct=EBI-297353, EBI-517684; CC P00533; Q9UQC2: GAB2; NbExp=3; IntAct=EBI-297353, EBI-975200; CC P00533; P60520: GABARAPL2; NbExp=3; IntAct=EBI-297353, EBI-720116; CC P00533; P47869: GABRA2; NbExp=2; IntAct=EBI-297353, EBI-2685723; CC P00533; P04406: GAPDH; NbExp=7; IntAct=EBI-297353, EBI-354056; CC P00533; Q8NBJ4: GOLM1; NbExp=13; IntAct=EBI-297353, EBI-712073; CC P00533; Q14956: GPNMB; NbExp=3; IntAct=EBI-297353, EBI-7250369; CC P00533; Q14956-1: GPNMB; NbExp=2; IntAct=EBI-297353, EBI-16191078; CC P00533; O75791: GRAP2; NbExp=3; IntAct=EBI-297353, EBI-740418; CC P00533; Q13322: GRB10; NbExp=3; IntAct=EBI-297353, EBI-80275; CC P00533; P62993: GRB2; NbExp=48; IntAct=EBI-297353, EBI-401755; CC P00533; Q99075: HBEGF; NbExp=3; IntAct=EBI-297353, EBI-7211558; CC P00533; P08631: HCK; NbExp=3; IntAct=EBI-297353, EBI-346340; CC P00533; Q9UBN7: HDAC6; NbExp=12; IntAct=EBI-297353, EBI-301697; CC P00533; Q8WUI4: HDAC7; NbExp=3; IntAct=EBI-297353, EBI-1048378; CC P00533; P07900: HSP90AA1; NbExp=7; IntAct=EBI-297353, EBI-296047; CC P00533; P08238: HSP90AB1; NbExp=10; IntAct=EBI-297353, EBI-352572; CC P00533; Q6PK50: HSP90AB1; NbExp=2; IntAct=EBI-297353, EBI-9356629; CC P00533; P08107: HSPA1B; NbExp=6; IntAct=EBI-297353, EBI-629985; CC P00533; P34932: HSPA4; NbExp=3; IntAct=EBI-297353, EBI-356933; CC P00533; P11142: HSPA8; NbExp=7; IntAct=EBI-297353, EBI-351896; CC P00533; P38646: HSPA9; NbExp=5; IntAct=EBI-297353, EBI-354932; CC P00533; P17936: IGFBP3; NbExp=3; IntAct=EBI-297353, EBI-715709; CC P00533; P46940: IQGAP1; NbExp=4; IntAct=EBI-297353, EBI-297509; CC P00533; O14654: IRS4; NbExp=2; IntAct=EBI-297353, EBI-356594; CC P00533; Q9NZM3: ITSN2; NbExp=3; IntAct=EBI-297353, EBI-308689; CC P00533; P14923: JUP; NbExp=3; IntAct=EBI-297353, EBI-702484; CC P00533; Q86VI4: LAPTM4B; NbExp=10; IntAct=EBI-297353, EBI-3267258; CC P00533; O43561: LAT; NbExp=3; IntAct=EBI-297353, EBI-1222766; CC P00533; Q13094: LCP2; NbExp=3; IntAct=EBI-297353, EBI-346946; CC P00533; Q96FE5: LINGO1; NbExp=2; IntAct=EBI-297353, EBI-719955; CC P00533; Q96JA1: LRIG1; NbExp=6; IntAct=EBI-297353, EBI-2865191; CC P00533; O94898: LRIG2; NbExp=4; IntAct=EBI-297353, EBI-2830372; CC P00533; Q38SD2: LRRK1; NbExp=2; IntAct=EBI-297353, EBI-1050422; CC P00533; P07948: LYN; NbExp=7; IntAct=EBI-297353, EBI-79452; CC P00533; P07948-1: LYN; NbExp=2; IntAct=EBI-297353, EBI-6895930; CC P00533; Q9BRK4: LZTS2; NbExp=2; IntAct=EBI-297353, EBI-741037; CC P00533; Q12852: MAP3K12; NbExp=3; IntAct=EBI-297353, EBI-710223; CC P00533; Q9UQF2: MAPK8IP1; NbExp=3; IntAct=EBI-297353, EBI-78404; CC P00533; Q13387: MAPK8IP2; NbExp=5; IntAct=EBI-297353, EBI-722813; CC P00533; Q9Y2H9: MAST1; NbExp=3; IntAct=EBI-297353, EBI-3385920; CC P00533; Q9NS73: MBIP; NbExp=2; IntAct=EBI-297353, EBI-741953; CC P00533; P08581: MET; NbExp=8; IntAct=EBI-297353, EBI-1039152; CC P00533; P14174: MIF; NbExp=3; IntAct=EBI-297353, EBI-372712; CC P00533; P15941: MUC1; NbExp=4; IntAct=EBI-297353, EBI-2804728; CC P00533; P16333: NCK1; NbExp=5; IntAct=EBI-297353, EBI-389883; CC P00533; P46934: NEDD4; NbExp=3; IntAct=EBI-297353, EBI-726944; CC P00533; P04150: NR3C1; NbExp=3; IntAct=EBI-297353, EBI-493507; CC P00533; P49757: NUMB; NbExp=2; IntAct=EBI-297353, EBI-915016; CC P00533; Q9Y6R0: NUMBL; NbExp=2; IntAct=EBI-297353, EBI-945925; CC P00533; Q13438: OS9; NbExp=3; IntAct=EBI-297353, EBI-725454; CC P00533; P16234: PDGFRA; NbExp=4; IntAct=EBI-297353, EBI-2861522; CC P00533; O00750: PIK3C2B; NbExp=10; IntAct=EBI-297353, EBI-641107; CC P00533; P27986: PIK3R1; NbExp=6; IntAct=EBI-297353, EBI-79464; CC P00533; O00459: PIK3R2; NbExp=5; IntAct=EBI-297353, EBI-346930; CC P00533; Q92569: PIK3R3; NbExp=7; IntAct=EBI-297353, EBI-79893; CC P00533; P19174: PLCG1; NbExp=6; IntAct=EBI-297353, EBI-79387; CC P00533; P16885: PLCG2; NbExp=6; IntAct=EBI-297353, EBI-617403; CC P00533; P35813: PPM1A; NbExp=2; IntAct=EBI-297353, EBI-989143; CC P00533; P17252: PRKCA; NbExp=3; IntAct=EBI-297353, EBI-1383528; CC P00533; Q05397: PTK2; NbExp=7; IntAct=EBI-297353, EBI-702142; CC P00533; P18031: PTPN1; NbExp=9; IntAct=EBI-297353, EBI-968788; CC P00533; Q06124: PTPN11; NbExp=5; IntAct=EBI-297353, EBI-297779; CC P00533; Q05209: PTPN12; NbExp=5; IntAct=EBI-297353, EBI-2266035; CC P00533; Q9Y2R2: PTPN22; NbExp=3; IntAct=EBI-297353, EBI-1211241; CC P00533; P18433: PTPRA; NbExp=3; IntAct=EBI-297353, EBI-2609645; CC P00533; P23467: PTPRB; NbExp=3; IntAct=EBI-297353, EBI-1265766; CC P00533; P08575: PTPRC; NbExp=2; IntAct=EBI-297353, EBI-1341; CC P00533; P23470: PTPRG; NbExp=3; IntAct=EBI-297353, EBI-2258115; CC P00533; Q9HD43: PTPRH; NbExp=3; IntAct=EBI-297353, EBI-1267176; CC P00533; Q9UJ41: RABGEF1; NbExp=4; IntAct=EBI-297353, EBI-913954; CC P00533; Q70E73: RAPH1; NbExp=2; IntAct=EBI-297353, EBI-3940924; CC P00533; P20936: RASA1; NbExp=7; IntAct=EBI-297353, EBI-1026476; CC P00533; Q13671: RIN1; NbExp=3; IntAct=EBI-297353, EBI-366017; CC P00533; Q01973: ROR1; NbExp=8; IntAct=EBI-297353, EBI-6082337; CC P00533; Q92622: RUBCN; NbExp=3; IntAct=EBI-297353, EBI-2952709; CC P00533; P26447: S100A4; NbExp=6; IntAct=EBI-297353, EBI-717058; CC P00533; P61619: SEC61A1; NbExp=2; IntAct=EBI-297353, EBI-358919; CC P00533; Q9UBV2: SEL1L; NbExp=2; IntAct=EBI-297353, EBI-358766; CC P00533; P31947: SFN; NbExp=9; IntAct=EBI-297353, EBI-476295; CC P00533; Q9NRF2: SH2B1; NbExp=4; IntAct=EBI-297353, EBI-310491; CC P00533; Q9UQQ2: SH2B3; NbExp=2; IntAct=EBI-297353, EBI-7879749; CC P00533; Q9BRG2: SH2D3A; NbExp=3; IntAct=EBI-297353, EBI-2339271; CC P00533; P29353: SHC1; NbExp=37; IntAct=EBI-297353, EBI-78835; CC P00533; P29353-7: SHC1; NbExp=4; IntAct=EBI-297353, EBI-9691288; CC P00533; P98077: SHC2; NbExp=3; IntAct=EBI-297353, EBI-7256023; CC P00533; Q6S5L8: SHC4; NbExp=3; IntAct=EBI-297353, EBI-9453524; CC P00533; O75563: SKAP2; NbExp=2; IntAct=EBI-297353, EBI-2483161; CC P00533; Q13239: SLA; NbExp=3; IntAct=EBI-297353, EBI-726214; CC P00533; P13866: SLC5A1; NbExp=3; IntAct=EBI-297353, EBI-1772443; CC P00533; Q07889: SOS1; NbExp=3; IntAct=EBI-297353, EBI-297487; CC P00533; P12931: SRC; NbExp=9; IntAct=EBI-297353, EBI-621482; CC P00533; P42224: STAT1; NbExp=7; IntAct=EBI-297353, EBI-1057697; CC P00533; P40763: STAT3; NbExp=15; IntAct=EBI-297353, EBI-518675; CC P00533; P42229: STAT5A; NbExp=4; IntAct=EBI-297353, EBI-749537; CC P00533; P31948: STIP1; NbExp=3; IntAct=EBI-297353, EBI-1054052; CC P00533; Q9UNE7: STUB1; NbExp=4; IntAct=EBI-297353, EBI-357085; CC P00533; O43752: STX6; NbExp=3; IntAct=EBI-297353, EBI-2695795; CC P00533; P43405: SYK; NbExp=6; IntAct=EBI-297353, EBI-78302; CC P00533; Q15750: TAB1; NbExp=3; IntAct=EBI-297353, EBI-358643; CC P00533; Q9Y6A5: TACC3; NbExp=3; IntAct=EBI-297353, EBI-2554984; CC P00533; P01135: TGFA; NbExp=4; IntAct=EBI-297353, EBI-1034374; CC P00533; Q9Y490: TLN1; NbExp=2; IntAct=EBI-297353, EBI-2462036; CC P00533; O60603: TLR2; NbExp=3; IntAct=EBI-297353, EBI-973722; CC P00533; Q9Y6Q6-2: TNFRSF11A; NbExp=3; IntAct=EBI-297353, EBI-20899422; CC P00533; Q68CZ2: TNS3; NbExp=5; IntAct=EBI-297353, EBI-1220488; CC P00533; Q8IZW8: TNS4; NbExp=2; IntAct=EBI-297353, EBI-7543499; CC P00533; O75674: TOM1L1; NbExp=6; IntAct=EBI-297353, EBI-712991; CC P00533; Q12933: TRAF2; NbExp=4; IntAct=EBI-297353, EBI-355744; CC P00533; Q71U36: TUBA1A; NbExp=4; IntAct=EBI-297353, EBI-302552; CC P00533; Q13885: TUBB2A; NbExp=2; IntAct=EBI-297353, EBI-711595; CC P00533; P10599: TXN; NbExp=5; IntAct=EBI-297353, EBI-594644; CC P00533; P09936: UCHL1; NbExp=3; IntAct=EBI-297353, EBI-714860; CC P00533; Q8TEY7: USP33; NbExp=2; IntAct=EBI-297353, EBI-719283; CC P00533; Q9P0L0: VAPA; NbExp=4; IntAct=EBI-297353, EBI-1059156; CC P00533; P07947: YES1; NbExp=3; IntAct=EBI-297353, EBI-515331; CC P00533; P27348: YWHAQ; NbExp=7; IntAct=EBI-297353, EBI-359854; CC P00533; P63104: YWHAZ; NbExp=6; IntAct=EBI-297353, EBI-347088; CC P00533; P43403: ZAP70; NbExp=3; IntAct=EBI-297353, EBI-1211276; CC P00533; Q53FC7; NbExp=3; IntAct=EBI-297353, EBI-9356749; CC P00533; Q96BE0; NbExp=2; IntAct=EBI-297353, EBI-9356686; CC P00533; P62161: Calm3; Xeno; NbExp=6; IntAct=EBI-297353, EBI-397530; CC P00533; P22682: Cbl; Xeno; NbExp=2; IntAct=EBI-297353, EBI-640919; CC P00533; Q9QZC5: Grb7; Xeno; NbExp=7; IntAct=EBI-297353, EBI-22085551; CC P00533; P97313: Prkdc; Xeno; NbExp=4; IntAct=EBI-297353, EBI-2272005; CC P00533; P20417: Ptpn1; Xeno; NbExp=11; IntAct=EBI-297353, EBI-916819; CC P00533; Q80U62: Rubcn; Xeno; NbExp=2; IntAct=EBI-297353, EBI-3506572; CC P00533; P0DTC2: S; Xeno; NbExp=4; IntAct=EBI-297353, EBI-25474821; CC P00533; Q8K424: Trpv3; Xeno; NbExp=2; IntAct=EBI-297353, EBI-2650739; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17182860, CC ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:23589287, CC ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960}; Single-pass CC type I membrane protein {ECO:0000269|PubMed:27153536}. Endoplasmic CC reticulum membrane {ECO:0000269|PubMed:27153536}; Single-pass type I CC membrane protein. Golgi apparatus membrane; Single-pass type I membrane CC protein. Nucleus membrane; Single-pass type I membrane protein. CC Endosome {ECO:0000269|PubMed:17182860, ECO:0000269|PubMed:27153536}. CC Endosome membrane. Nucleus {ECO:0000269|PubMed:17115032, CC ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:20551055, CC ECO:0000269|PubMed:20674546}. Note=In response to EGF, translocated CC from the cell membrane to the nucleus via Golgi and ER CC (PubMed:20674546, PubMed:17909029). Endocytosed upon activation by CC ligand (PubMed:2790960, PubMed:17182860, PubMed:27153536, CC PubMed:17909029). Colocalized with GPER1 in the nucleus of estrogen CC agonist-induced cancer-associated fibroblasts (CAF) (PubMed:20551055). CC {ECO:0000269|PubMed:17182860, ECO:0000269|PubMed:17909029, CC ECO:0000269|PubMed:20674546, ECO:0000269|PubMed:27153536, CC ECO:0000269|PubMed:2790960}. 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: Ubiquitously expressed. Isoform 2 is also expressed CC in ovarian cancers. {ECO:0000269|PubMed:17671655}. CC -!- PTM: Phosphorylated on Tyr residues in response to EGF CC (PubMed:20462955, PubMed:27153536). Phosphorylation at Ser-695 is CC partial and occurs only if Thr-693 is phosphorylated. Phosphorylation CC at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced MAPK8/JNK1 CC activation. Dephosphorylation by PTPRJ prevents endocytosis and CC stabilizes the receptor at the plasma membrane. Autophosphorylation at CC Tyr-1197 is stimulated by methylation at Arg-1199 and enhances CC interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 CC recruits STAT3. Dephosphorylated by PTPN1 and PTPN2. CC {ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:12873986, CC ECO:0000269|PubMed:16083266, ECO:0000269|PubMed:19563760, CC ECO:0000269|PubMed:19836242, ECO:0000269|PubMed:20462955, CC ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:2543678, CC ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:3138233}. CC -!- PTM: Monoubiquitinated and polyubiquitinated upon EGF stimulation; CC which does not affect tyrosine kinase activity or signaling capacity CC but may play a role in lysosomal targeting (PubMed:27153536). CC Polyubiquitin linkage is mainly through 'Lys-63', but linkage through CC 'Lys-48', 'Lys-11' and 'Lys-29' also occurs. Deubiquitination by OTUD7B CC prevents degradation. Ubiquitinated by RNF115 and RNF126 (By CC similarity). Ubiquitinated by ZNRF1 or CBL at different lysines in CC response to EGF stimulation; leading to recruitment of the ESCRT CC machinery and subsequent degradation in the lysosomes CC (PubMed:33996800). Deubiquitinated by UCHL1 leading to the inhibition CC of its degradation (By similarity). {ECO:0000250|UniProtKB:Q01279, CC ECO:0000269|PubMed:16543144, ECO:0000269|PubMed:22179831, CC ECO:0000269|PubMed:22298428, ECO:0000269|PubMed:27153536, CC ECO:0000269|PubMed:33996800}. CC -!- PTM: Palmitoylated on Cys residues by ZDHHC20. Palmitoylation inhibits CC internalization after ligand binding, and increases the persistence of CC tyrosine-phosphorylated EGFR at the cell membrane. Palmitoylation CC increases the amplitude and duration of EGFR signaling. CC {ECO:0000269|PubMed:27153536}. CC -!- PTM: Methylated. Methylation at Arg-1199 by PRMT5 stimulates CC phosphorylation at Tyr-1197. {ECO:0000269|PubMed:19563760, CC ECO:0000269|PubMed:19836242, ECO:0000269|PubMed:21258366}. CC -!- DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting CC tissues of the lung. The most common form of lung cancer is non-small CC cell lung cancer (NSCLC) that can be divided into 3 major histologic CC subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung CC cancer. NSCLC is often diagnosed at an advanced stage and has a poor CC prognosis. {ECO:0000269|PubMed:15118125, ECO:0000269|PubMed:16533793, CC ECO:0000269|PubMed:16672372}. Note=The gene represented in this entry CC is involved in disease pathogenesis. CC -!- DISEASE: Inflammatory skin and bowel disease, neonatal, 2 (NISBD2) CC [MIM:616069]: A disorder characterized by inflammatory features with CC neonatal onset, involving the skin, hair, and gut. The skin lesions CC involve perioral and perianal erythema, psoriasiform erythroderma, with CC flares of erythema, scaling, and widespread pustules. Gastrointestinal CC symptoms include malabsorptive diarrhea that is exacerbated by CC intercurrent gastrointestinal infections. The hair is short or broken, CC and the eyelashes and eyebrows are wiry and disorganized. CC {ECO:0000269|PubMed:24691054}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. EGF receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/egfr/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=EGFR entry; CC URL="https://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_DNA. DR EMBL; U48725; AAC50797.1; -; Genomic_DNA. DR EMBL; U48726; AAC50798.1; -; Genomic_DNA. DR EMBL; U48727; AAC50799.1; -; Genomic_DNA. DR EMBL; U48728; AAC50800.1; -; Genomic_DNA. DR EMBL; U48729; AAC50801.1; -; Genomic_DNA. 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; AY698024; AAT97979.1; -; mRNA. 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 CCDS; CCDS47587.1; -. [P00533-2] DR CCDS; CCDS5514.1; -. [P00533-1] DR CCDS; CCDS5515.1; -. [P00533-3] DR CCDS; CCDS5516.1; -. [P00533-4] DR PIR; A00641; GQHUE. DR RefSeq; NP_005219.2; NM_005228.4. [P00533-1] DR RefSeq; NP_958439.1; NM_201282.1. [P00533-4] DR RefSeq; NP_958440.1; NM_201283.1. [P00533-2] DR RefSeq; NP_958441.1; NM_201284.1. [P00533-3] 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; 2EB2; X-ray; 2.50 A; A=695-1022. DR PDB; 2EB3; X-ray; 2.84 A; A=695-1022. DR PDB; 2GS2; X-ray; 2.80 A; A=696-1022. DR PDB; 2GS6; X-ray; 2.60 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; 2.72 A; A=696-1022. DR PDB; 2J5E; X-ray; 3.10 A; A=696-1022. DR PDB; 2J5F; X-ray; 3.00 A; A=696-1022. DR PDB; 2J6M; X-ray; 3.10 A; A=696-1022. DR PDB; 2JIT; X-ray; 3.10 A; A/B=696-1022. DR PDB; 2JIU; X-ray; 3.05 A; A/B=695-1022. DR PDB; 2JIV; X-ray; 3.50 A; A/B=695-1022. DR PDB; 2KS1; NMR; -; B=634-677. DR PDB; 2M0B; NMR; -; A/B=634-677. DR PDB; 2M20; NMR; -; A/B=642-697. DR PDB; 2N5S; NMR; -; A=642-690. DR PDB; 2RF9; X-ray; 3.50 A; A/B=696-1022. DR PDB; 2RFD; X-ray; 3.60 A; A/B=702-1022. DR PDB; 2RFE; X-ray; 2.90 A; A/B/C/D=702-1022. DR PDB; 2RGP; X-ray; 2.00 A; A=702-1016. DR PDB; 3B2U; X-ray; 2.58 A; A/B/E/I/M/P/S/V=335-538. DR PDB; 3B2V; X-ray; 3.30 A; A=25-642. DR PDB; 3BEL; X-ray; 2.30 A; A=702-1016. DR PDB; 3BUO; X-ray; 2.60 A; A/C=1063-1075. DR PDB; 3C09; X-ray; 3.20 A; A/D=336-538. DR PDB; 3G5V; X-ray; 2.00 A; C=311-326. DR PDB; 3G5Y; X-ray; 1.59 A; E=311-326. DR PDB; 3GOP; X-ray; 2.80 A; A=669-1022. DR PDB; 3GT8; X-ray; 2.96 A; A/B/C/D=696-1022. DR PDB; 3IKA; X-ray; 2.90 A; A/B=694-1022. DR PDB; 3LZB; X-ray; 2.70 A; A/B/C/D/E/F/G/H=696-983. DR PDB; 3NJP; X-ray; 3.30 A; A/B=25-638. DR PDB; 3OB2; X-ray; 2.10 A; A=1063-1074. DR PDB; 3OP0; X-ray; 2.52 A; C/D=1066-1076. DR PDB; 3P0Y; X-ray; 1.80 A; A=334-538. DR PDB; 3PFV; X-ray; 2.27 A; C/D=1066-1076. DR PDB; 3POZ; X-ray; 1.50 A; A=696-1022. DR PDB; 3QWQ; X-ray; 2.75 A; A=1-642. DR PDB; 3UG1; X-ray; 2.75 A; A=695-1022. DR PDB; 3UG2; X-ray; 2.50 A; A=695-1022. DR PDB; 3VJN; X-ray; 2.34 A; A=695-1022. DR PDB; 3VJO; X-ray; 2.64 A; A=695-1022. DR PDB; 3VRP; X-ray; 1.52 A; B=1062-1074. DR PDB; 3VRR; X-ray; 2.00 A; C=1062-1074. DR PDB; 3W2O; X-ray; 2.35 A; A=698-1022. DR PDB; 3W2P; X-ray; 2.05 A; A=698-1022. DR PDB; 3W2Q; X-ray; 2.20 A; A=698-1022. DR PDB; 3W2R; X-ray; 2.05 A; A=698-1022. DR PDB; 3W2S; X-ray; 1.90 A; A=696-1022. DR PDB; 3W32; X-ray; 1.80 A; A=696-1022. DR PDB; 3W33; X-ray; 1.70 A; A=696-1022. DR PDB; 4G5J; X-ray; 2.80 A; A=696-1022. DR PDB; 4G5P; X-ray; 3.17 A; A/B=696-1022. DR PDB; 4HJO; X-ray; 2.75 A; A=696-1022. DR PDB; 4I1Z; X-ray; 3.00 A; A=695-1022. DR PDB; 4I20; X-ray; 3.34 A; A=695-1022. DR PDB; 4I21; X-ray; 3.37 A; A/B=695-1022. DR PDB; 4I22; X-ray; 1.71 A; A=695-1022. DR PDB; 4I23; X-ray; 2.80 A; A=695-1022. DR PDB; 4I24; X-ray; 1.80 A; A/B=695-1022. DR PDB; 4JQ7; X-ray; 2.73 A; A=696-1021. DR PDB; 4JQ8; X-ray; 2.83 A; A=696-1021. DR PDB; 4JR3; X-ray; 2.70 A; A=696-1021. DR PDB; 4JRV; X-ray; 2.80 A; A=696-1021. DR PDB; 4KRL; X-ray; 2.85 A; A=335-538. DR PDB; 4KRM; X-ray; 2.66 A; A/C/E/G/I/K=335-538. DR PDB; 4KRO; X-ray; 3.05 A; A=25-642. DR PDB; 4KRP; X-ray; 2.82 A; A=25-642. DR PDB; 4LI5; X-ray; 2.64 A; A=696-1020. DR PDB; 4LL0; X-ray; 4.00 A; A/B=694-1022. DR PDB; 4LQM; X-ray; 2.50 A; A=694-1022. DR PDB; 4LRM; X-ray; 3.53 A; A/B/C/D/E=694-1022. DR PDB; 4R3P; X-ray; 2.90 A; A=696-1018. DR PDB; 4R3R; X-ray; 3.25 A; A=696-1018. DR PDB; 4R5S; X-ray; 3.00 A; A=696-1022. DR PDB; 4RIW; X-ray; 3.10 A; B/D=682-1022. DR PDB; 4RIX; X-ray; 3.10 A; B/D=682-1022. DR PDB; 4RIY; X-ray; 2.98 A; B/D=682-1022. DR PDB; 4RJ4; X-ray; 2.78 A; A=695-1022. DR PDB; 4RJ5; X-ray; 3.10 A; A=695-1022. DR PDB; 4RJ6; X-ray; 2.70 A; A=695-1022. DR PDB; 4RJ7; X-ray; 2.55 A; A=695-1022. DR PDB; 4RJ8; X-ray; 2.50 A; A=695-1022. DR PDB; 4TKS; X-ray; 3.20 A; A=695-1022. DR PDB; 4UIP; X-ray; 2.95 A; A=26-637. DR PDB; 4UV7; X-ray; 2.10 A; A=25-645. DR PDB; 4WD5; X-ray; 3.30 A; A/B=694-1022. DR PDB; 4WKQ; X-ray; 1.85 A; A=696-1022. DR PDB; 4WRG; X-ray; 1.90 A; A=696-1022. DR PDB; 4ZAU; X-ray; 2.80 A; A=696-1022. DR PDB; 4ZJV; X-ray; 2.70 A; A/B=695-1022. DR PDB; 4ZSE; X-ray; 1.97 A; A/B/C/D=695-1022. DR PDB; 5C8K; X-ray; 3.00 A; A=695-1022. DR PDB; 5C8M; X-ray; 2.90 A; A=695-1022. DR PDB; 5C8N; X-ray; 2.40 A; A=695-1022. DR PDB; 5CAL; X-ray; 2.70 A; A=695-1022. DR PDB; 5CAN; X-ray; 2.80 A; A=695-1022. DR PDB; 5CAO; X-ray; 2.60 A; A=695-1022. DR PDB; 5CAP; X-ray; 2.40 A; A=695-1022. DR PDB; 5CAQ; X-ray; 2.50 A; A=695-1022. DR PDB; 5CAS; X-ray; 2.10 A; A=695-1022. DR PDB; 5CAU; X-ray; 2.25 A; A=695-1022. DR PDB; 5CAV; X-ray; 2.73 A; A=695-1022. DR PDB; 5CNN; X-ray; 1.90 A; A/B=696-1042. DR PDB; 5CNO; X-ray; 1.55 A; A/B/X=696-1022. DR PDB; 5CZH; X-ray; 2.80 A; A=694-1022. DR PDB; 5CZI; X-ray; 2.60 A; A=694-1022. DR PDB; 5D41; X-ray; 2.31 A; A/B=695-1022. DR PDB; 5EDP; X-ray; 2.90 A; A=695-1022. DR PDB; 5EDQ; X-ray; 2.80 A; A=695-1022. DR PDB; 5EDR; X-ray; 2.60 A; A=695-1022. DR PDB; 5EM5; X-ray; 2.65 A; A=695-1022. DR PDB; 5EM6; X-ray; 2.78 A; A=695-1022. DR PDB; 5EM7; X-ray; 2.81 A; A=695-1022. DR PDB; 5EM8; X-ray; 2.80 A; A=695-1022. DR PDB; 5FED; X-ray; 2.65 A; A=696-1022. DR PDB; 5FEE; X-ray; 2.70 A; A=696-1022. DR PDB; 5FEQ; X-ray; 3.40 A; A=696-1022. DR PDB; 5GMP; X-ray; 2.80 A; A=696-1022. DR PDB; 5GNK; X-ray; 1.80 A; A=696-988. DR PDB; 5GTY; X-ray; 3.14 A; A/B/C/D/E/F/G/H=696-1022. DR PDB; 5GTZ; X-ray; 3.00 A; A=696-1022. DR PDB; 5HCX; X-ray; 2.60 A; A=696-1022. DR PDB; 5HCY; X-ray; 2.46 A; A=696-1022. DR PDB; 5HCZ; X-ray; 2.62 A; A=696-1022. DR PDB; 5HG5; X-ray; 1.52 A; A=695-1022. DR PDB; 5HG7; X-ray; 1.85 A; A=695-1022. DR PDB; 5HG8; X-ray; 1.42 A; A=695-1022. DR PDB; 5HG9; X-ray; 2.15 A; A=695-1022. DR PDB; 5HIB; X-ray; 2.85 A; A=695-1022. DR PDB; 5HIC; X-ray; 2.60 A; A=695-1022. DR PDB; 5J9Y; X-ray; 2.80 A; A=697-1019. DR PDB; 5J9Z; X-ray; 2.50 A; A=696-1020. DR PDB; 5JEB; X-ray; 3.30 A; A=696-1022. DR PDB; 5LV6; NMR; -; A/B=634-677. DR PDB; 5SX4; X-ray; 2.80 A; M/N=335-525. DR PDB; 5SX5; X-ray; 2.50 A; M/N=335-525. DR PDB; 5U8L; X-ray; 1.60 A; A=695-1022. DR PDB; 5UG8; X-ray; 1.46 A; A=695-1022. DR PDB; 5UG9; X-ray; 1.33 A; A=695-1022. DR PDB; 5UGA; X-ray; 1.82 A; A=695-1022. DR PDB; 5UGB; X-ray; 2.53 A; A=695-1022. DR PDB; 5UGC; X-ray; 1.58 A; A=695-1022. DR PDB; 5UWD; X-ray; 3.06 A; A=695-1022. DR PDB; 5WB7; X-ray; 2.94 A; A/B/C/D=25-525. DR PDB; 5WB8; X-ray; 3.00 A; A/D=25-525. DR PDB; 5X26; X-ray; 2.95 A; A=696-1022. DR PDB; 5X27; X-ray; 2.95 A; A=696-1022. DR PDB; 5X28; X-ray; 2.95 A; A=696-1022. DR PDB; 5X2A; X-ray; 1.85 A; A/B/C/D=696-1022. DR PDB; 5X2C; X-ray; 2.05 A; A/B=696-1022. DR PDB; 5X2F; X-ray; 2.20 A; A/B/C/D=696-1022. DR PDB; 5X2K; X-ray; 3.20 A; A=696-1022. DR PDB; 5XDK; X-ray; 2.35 A; A=696-1022. DR PDB; 5XDL; X-ray; 2.70 A; A=696-1022. DR PDB; 5XGM; X-ray; 2.95 A; A=696-1022. DR PDB; 5XGN; X-ray; 3.00 A; A/B=696-1022. DR PDB; 5XWD; X-ray; 2.89 A; A=1-643. DR PDB; 5Y25; X-ray; 3.10 A; A=698-1022. DR PDB; 5Y9T; X-ray; 3.25 A; A=695-1022. DR PDB; 5YU9; X-ray; 1.95 A; A/B/C/D=696-1022. DR PDB; 5ZTO; X-ray; 2.65 A; A=696-1022. DR PDB; 5ZWJ; X-ray; 2.90 A; A=675-1022. DR PDB; 6ARU; X-ray; 3.20 A; A=25-640. DR PDB; 6B3S; X-ray; 2.80 A; A/B/E/I=335-538. DR PDB; 6D8E; X-ray; 2.54 A; A=696-1022. DR PDB; 6DUK; X-ray; 2.20 A; A/B/C/D/E/F=695-1022. DR PDB; 6JRJ; X-ray; 2.94 A; A=696-1022. DR PDB; 6JRK; X-ray; 2.80 A; A=696-1022. DR PDB; 6JRX; X-ray; 2.20 A; A=696-1022. DR PDB; 6JWL; X-ray; 2.55 A; A=696-1022. DR PDB; 6JX0; X-ray; 2.53 A; A=696-1022. DR PDB; 6JX4; X-ray; 2.53 A; A=696-1022. DR PDB; 6JXT; X-ray; 2.31 A; A=696-1022. DR PDB; 6JZ0; X-ray; 2.86 A; A=696-1021. DR PDB; 6LUB; X-ray; 2.31 A; A=695-1022. DR PDB; 6LUD; X-ray; 2.05 A; A=695-1022. DR PDB; 6P1D; X-ray; 2.40 A; A/B/C/D=696-1022. DR PDB; 6P1L; X-ray; 2.80 A; A/B/C/D=696-1022. DR PDB; 6P8Q; X-ray; 1.90 A; A/B/C/D=696-1022. DR PDB; 6S89; X-ray; 2.70 A; A=695-1022. DR PDB; 6S8A; X-ray; 2.60 A; A=695-1022. DR PDB; 6S9B; X-ray; 3.25 A; A=697-1022. DR PDB; 6S9C; X-ray; 2.73 A; A=696-1022. DR PDB; 6S9D; X-ray; 2.67 A; A=696-1022. DR PDB; 6TFU; X-ray; 2.00 A; A/B=695-1022. DR PDB; 6TFV; X-ray; 1.50 A; A/B=695-1022. DR PDB; 6TFW; X-ray; 2.00 A; A/B=695-1022. DR PDB; 6TFY; X-ray; 1.70 A; A/B=695-1022. DR PDB; 6TFZ; X-ray; 1.80 A; A/B=695-1022. DR PDB; 6TG0; X-ray; 1.50 A; A/B=695-1022. DR PDB; 6TG1; X-ray; 1.60 A; A/B=695-1022. DR PDB; 6V5N; X-ray; 2.40 A; A/B/C/D=695-1022. DR PDB; 6V5P; X-ray; 2.30 A; A/B/C/D=695-1022. DR PDB; 6V66; X-ray; 1.79 A; A/B/C/D=696-1022. DR PDB; 6V6K; X-ray; 2.20 A; A/B/C/D/E/F/G/H=696-1022. DR PDB; 6V6O; X-ray; 2.10 A; A/B/C/D/E/F/G/H=696-1022. DR PDB; 6VH4; X-ray; 2.80 A; A=696-1022. DR PDB; 6VHN; X-ray; 2.40 A; A=696-1022. DR PDB; 6VHP; X-ray; 3.60 A; A=696-1022. DR PDB; 6WA2; X-ray; 2.40 A; A/B/C/D=695-1022. DR PDB; 6WAK; X-ray; 2.40 A; A/B/C/D=695-1022. DR PDB; 6WXN; X-ray; 1.76 A; A/B/C/D=695-1022. DR PDB; 6XL4; X-ray; 2.06 A; A/B/C/D=695-1022. DR PDB; 6Z4B; X-ray; 2.50 A; A/B=695-1022. DR PDB; 6Z4D; X-ray; 2.00 A; A/B=695-1022. DR PDB; 7A2A; X-ray; 1.90 A; A/B=695-1022. DR PDB; 7A6I; X-ray; 2.40 A; A=695-1022. DR PDB; 7A6J; X-ray; 2.00 A; A/B=695-1022. DR PDB; 7A6K; X-ray; 2.00 A; A/B/C/D=695-1022. DR PDB; 7AEI; X-ray; 2.65 A; A=695-1022. DR PDB; 7AEM; X-ray; 2.65 A; A=695-1022. DR PDB; 7B85; X-ray; 2.50 A; A=695-1022. DR PDB; 7ER2; X-ray; 2.66 A; A=696-1022. DR PDB; 7JXI; X-ray; 3.00 A; A/B/C/D=695-1022. DR PDB; 7JXK; X-ray; 3.10 A; A/B/C/D/E/F=695-1022. DR PDB; 7JXL; X-ray; 2.40 A; A/B/C/D=695-1022. DR PDB; 7JXM; X-ray; 2.19 A; A/B/C/D=695-1022. DR PDB; 7JXP; X-ray; 2.16 A; A/B/C/D/E/F=695-1022. DR PDB; 7JXQ; X-ray; 1.83 A; A/B/C/D=695-1022. DR PDB; 7JXW; X-ray; 2.50 A; A/B/C/D=695-1022. DR PDB; 7K1H; X-ray; 2.60 A; A/B/C/D/E/F=695-1022. DR PDB; 7K1I; X-ray; 3.20 A; A=695-1022. DR PDB; 7KXZ; X-ray; 2.40 A; A=695-1022. DR PDB; 7KY0; X-ray; 3.10 A; A/B/C/D=695-1022. DR PDB; 7LEN; X-ray; 2.90 A; A/B=25-525. DR PDB; 7LFR; X-ray; 3.20 A; A/B=25-525. DR PDB; 7LFS; X-ray; 3.50 A; A/B/C/D=25-525. DR PDB; 7LG8; X-ray; 2.93 A; A/B/C/D=695-1022. DR PDB; 7LGS; X-ray; 3.10 A; A/B/C/D=696-1022. DR PDB; 7LTX; X-ray; 2.30 A; A/B/C/D=695-1022. DR PDB; 7OM4; X-ray; 6.05 A; A=25-645. DR PDB; 7OXB; X-ray; 2.56 A; A=696-1020. DR PDB; 7SI1; X-ray; 1.60 A; A=695-1022. DR PDB; 7SYD; EM; 3.10 A; A/B=1-1210. DR PDB; 7SYE; EM; 3.30 A; A/B=1-1210. DR PDB; 7SZ0; EM; 3.30 A; A/B=1-1210. DR PDB; 7SZ1; EM; 3.40 A; A/B=1-1210. DR PDB; 7SZ5; EM; 3.60 A; A/B=1-1210. DR PDB; 7SZ7; EM; 3.40 A; A/B=1-1210. DR PDB; 7T4I; X-ray; 2.61 A; A=696-1022. DR PDB; 7T4J; X-ray; 2.20 A; A/B=696-1022. DR PDB; 7TVD; X-ray; 2.96 A; A=696-1022. DR PDB; 7U98; X-ray; 3.42 A; A/B/C/D=695-1022. DR PDB; 7U99; X-ray; 2.50 A; A=695-1022. DR PDB; 7U9A; X-ray; 2.60 A; A=695-1022. DR PDB; 7UKV; X-ray; 2.40 A; A=695-1022. DR PDB; 7UKW; X-ray; 2.60 A; A/B/C/D=695-1022. DR PDB; 7VRA; X-ray; 2.41 A; A=696-1022. DR PDB; 7VRE; X-ray; 2.51 A; A=696-1022. DR PDB; 7ZYM; X-ray; 2.50 A; A=695-1022. DR PDB; 7ZYN; X-ray; 2.30 A; A=695-1022. DR PDB; 7ZYP; X-ray; 2.80 A; A=695-1022. DR PDB; 7ZYQ; X-ray; 2.10 A; A/B=695-1022. DR PDB; 8A27; X-ray; 1.07 A; A=700-1022. DR PDB; 8A2A; X-ray; 1.43 A; A=700-1022. DR PDB; 8A2B; X-ray; 1.69 A; A=700-1022. DR PDB; 8A2D; X-ray; 1.11 A; A=700-1022. DR PDB; 8D73; X-ray; 2.17 A; A/B=695-1022. DR PDB; 8D76; X-ray; 2.40 A; A/B=695-1022. DR PDB; 8DSW; X-ray; 2.39 A; A=696-1022. DR PDB; 8EME; X-ray; 3.32 A; A/B=695-1022. DR PDB; 8F1H; X-ray; 2.80 A; A=695-1022. DR PDB; 8F1W; X-ray; 3.20 A; A/B/C/D=695-1022. DR PDB; 8F1X; X-ray; 2.30 A; A=695-1022. DR PDB; 8F1Y; X-ray; 2.75 A; A=695-1022. DR PDB; 8F1Z; X-ray; 2.40 A; A=695-1022. DR PDB; 8G63; X-ray; 2.50 A; A=696-1022. DR PDB; 8H7X; X-ray; 3.40 A; A/B=696-1022. DR PDB; 8HGO; EM; 3.31 A; A=1-683. DR PDB; 8HGP; EM; 4.53 A; A=1-683. DR PDB; 8HGS; EM; 3.81 A; A/B=1-683. DR PDB; 8HY7; X-ray; 2.91 A; A=695-1022. 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; 2EB2; -. DR PDBsum; 2EB3; -. DR PDBsum; 2GS2; -. DR PDBsum; 2GS6; -. 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; 2J5F; -. DR PDBsum; 2J6M; -. DR PDBsum; 2JIT; -. DR PDBsum; 2JIU; -. DR PDBsum; 2JIV; -. DR PDBsum; 2KS1; -. DR PDBsum; 2M0B; -. DR PDBsum; 2M20; -. DR PDBsum; 2N5S; -. DR PDBsum; 2RF9; -. DR PDBsum; 2RFD; -. DR PDBsum; 2RFE; -. DR PDBsum; 2RGP; -. DR PDBsum; 3B2U; -. DR PDBsum; 3B2V; -. DR PDBsum; 3BEL; -. DR PDBsum; 3BUO; -. DR PDBsum; 3C09; -. DR PDBsum; 3G5V; -. DR PDBsum; 3G5Y; -. DR PDBsum; 3GOP; -. DR PDBsum; 3GT8; -. DR PDBsum; 3IKA; -. DR PDBsum; 3LZB; -. DR PDBsum; 3NJP; -. DR PDBsum; 3OB2; -. DR PDBsum; 3OP0; -. DR PDBsum; 3P0Y; -. DR PDBsum; 3PFV; -. DR PDBsum; 3POZ; -. DR PDBsum; 3QWQ; -. DR PDBsum; 3UG1; -. DR PDBsum; 3UG2; -. DR PDBsum; 3VJN; -. DR PDBsum; 3VJO; -. DR PDBsum; 3VRP; -. DR PDBsum; 3VRR; -. DR PDBsum; 3W2O; -. DR PDBsum; 3W2P; -. DR PDBsum; 3W2Q; -. DR PDBsum; 3W2R; -. DR PDBsum; 3W2S; -. DR PDBsum; 3W32; -. DR PDBsum; 3W33; -. DR PDBsum; 4G5J; -. DR PDBsum; 4G5P; -. DR PDBsum; 4HJO; -. DR PDBsum; 4I1Z; -. DR PDBsum; 4I20; -. DR PDBsum; 4I21; -. DR PDBsum; 4I22; -. DR PDBsum; 4I23; -. DR PDBsum; 4I24; -. DR PDBsum; 4JQ7; -. DR PDBsum; 4JQ8; -. DR PDBsum; 4JR3; -. DR PDBsum; 4JRV; -. DR PDBsum; 4KRL; -. DR PDBsum; 4KRM; -. DR PDBsum; 4KRO; -. DR PDBsum; 4KRP; -. DR PDBsum; 4LI5; -. DR PDBsum; 4LL0; -. DR PDBsum; 4LQM; -. DR PDBsum; 4LRM; -. DR PDBsum; 4R3P; -. DR PDBsum; 4R3R; -. DR PDBsum; 4R5S; -. DR PDBsum; 4RIW; -. DR PDBsum; 4RIX; -. DR PDBsum; 4RIY; -. DR PDBsum; 4RJ4; -. DR PDBsum; 4RJ5; -. DR PDBsum; 4RJ6; -. DR PDBsum; 4RJ7; -. DR PDBsum; 4RJ8; -. DR PDBsum; 4TKS; -. DR PDBsum; 4UIP; -. DR PDBsum; 4UV7; -. DR PDBsum; 4WD5; -. DR PDBsum; 4WKQ; -. DR PDBsum; 4WRG; -. DR PDBsum; 4ZAU; -. DR PDBsum; 4ZJV; -. DR PDBsum; 4ZSE; -. DR PDBsum; 5C8K; -. DR PDBsum; 5C8M; -. DR PDBsum; 5C8N; -. DR PDBsum; 5CAL; -. DR PDBsum; 5CAN; -. DR PDBsum; 5CAO; -. DR PDBsum; 5CAP; -. DR PDBsum; 5CAQ; -. DR PDBsum; 5CAS; -. DR PDBsum; 5CAU; -. DR PDBsum; 5CAV; -. DR PDBsum; 5CNN; -. DR PDBsum; 5CNO; -. DR PDBsum; 5CZH; -. DR PDBsum; 5CZI; -. DR PDBsum; 5D41; -. DR PDBsum; 5EDP; -. DR PDBsum; 5EDQ; -. DR PDBsum; 5EDR; -. DR PDBsum; 5EM5; -. DR PDBsum; 5EM6; -. DR PDBsum; 5EM7; -. DR PDBsum; 5EM8; -. DR PDBsum; 5FED; -. DR PDBsum; 5FEE; -. DR PDBsum; 5FEQ; -. DR PDBsum; 5GMP; -. DR PDBsum; 5GNK; -. DR PDBsum; 5GTY; -. DR PDBsum; 5GTZ; -. DR PDBsum; 5HCX; -. DR PDBsum; 5HCY; -. DR PDBsum; 5HCZ; -. DR PDBsum; 5HG5; -. DR PDBsum; 5HG7; -. DR PDBsum; 5HG8; -. DR PDBsum; 5HG9; -. DR PDBsum; 5HIB; -. DR PDBsum; 5HIC; -. DR PDBsum; 5J9Y; -. DR PDBsum; 5J9Z; -. DR PDBsum; 5JEB; -. DR PDBsum; 5LV6; -. DR PDBsum; 5SX4; -. DR PDBsum; 5SX5; -. DR PDBsum; 5U8L; -. DR PDBsum; 5UG8; -. DR PDBsum; 5UG9; -. DR PDBsum; 5UGA; -. DR PDBsum; 5UGB; -. DR PDBsum; 5UGC; -. DR PDBsum; 5UWD; -. DR PDBsum; 5WB7; -. DR PDBsum; 5WB8; -. DR PDBsum; 5X26; -. DR PDBsum; 5X27; -. DR PDBsum; 5X28; -. DR PDBsum; 5X2A; -. DR PDBsum; 5X2C; -. DR PDBsum; 5X2F; -. DR PDBsum; 5X2K; -. DR PDBsum; 5XDK; -. DR PDBsum; 5XDL; -. DR PDBsum; 5XGM; -. DR PDBsum; 5XGN; -. DR PDBsum; 5XWD; -. DR PDBsum; 5Y25; -. DR PDBsum; 5Y9T; -. DR PDBsum; 5YU9; -. DR PDBsum; 5ZTO; -. DR PDBsum; 5ZWJ; -. DR PDBsum; 6ARU; -. DR PDBsum; 6B3S; -. DR PDBsum; 6D8E; -. DR PDBsum; 6DUK; -. DR PDBsum; 6JRJ; -. DR PDBsum; 6JRK; -. DR PDBsum; 6JRX; -. DR PDBsum; 6JWL; -. DR PDBsum; 6JX0; -. DR PDBsum; 6JX4; -. DR PDBsum; 6JXT; -. DR PDBsum; 6JZ0; -. DR PDBsum; 6LUB; -. DR PDBsum; 6LUD; -. DR PDBsum; 6P1D; -. DR PDBsum; 6P1L; -. DR PDBsum; 6P8Q; -. DR PDBsum; 6S89; -. DR PDBsum; 6S8A; -. DR PDBsum; 6S9B; -. DR PDBsum; 6S9C; -. DR PDBsum; 6S9D; -. DR PDBsum; 6TFU; -. DR PDBsum; 6TFV; -. DR PDBsum; 6TFW; -. DR PDBsum; 6TFY; -. DR PDBsum; 6TFZ; -. DR PDBsum; 6TG0; -. DR PDBsum; 6TG1; -. DR PDBsum; 6V5N; -. DR PDBsum; 6V5P; -. DR PDBsum; 6V66; -. DR PDBsum; 6V6K; -. DR PDBsum; 6V6O; -. DR PDBsum; 6VH4; -. DR PDBsum; 6VHN; -. DR PDBsum; 6VHP; -. DR PDBsum; 6WA2; -. DR PDBsum; 6WAK; -. DR PDBsum; 6WXN; -. DR PDBsum; 6XL4; -. DR PDBsum; 6Z4B; -. DR PDBsum; 6Z4D; -. DR PDBsum; 7A2A; -. DR PDBsum; 7A6I; -. DR PDBsum; 7A6J; -. DR PDBsum; 7A6K; -. DR PDBsum; 7AEI; -. DR PDBsum; 7AEM; -. DR PDBsum; 7B85; -. DR PDBsum; 7ER2; -. DR PDBsum; 7JXI; -. DR PDBsum; 7JXK; -. DR PDBsum; 7JXL; -. DR PDBsum; 7JXM; -. DR PDBsum; 7JXP; -. DR PDBsum; 7JXQ; -. DR PDBsum; 7JXW; -. DR PDBsum; 7K1H; -. DR PDBsum; 7K1I; -. DR PDBsum; 7KXZ; -. DR PDBsum; 7KY0; -. DR PDBsum; 7LEN; -. DR PDBsum; 7LFR; -. DR PDBsum; 7LFS; -. DR PDBsum; 7LG8; -. DR PDBsum; 7LGS; -. DR PDBsum; 7LTX; -. DR PDBsum; 7OM4; -. DR PDBsum; 7OXB; -. DR PDBsum; 7SI1; -. DR PDBsum; 7SYD; -. DR PDBsum; 7SYE; -. DR PDBsum; 7SZ0; -. DR PDBsum; 7SZ1; -. DR PDBsum; 7SZ5; -. DR PDBsum; 7SZ7; -. DR PDBsum; 7T4I; -. DR PDBsum; 7T4J; -. DR PDBsum; 7TVD; -. DR PDBsum; 7U98; -. DR PDBsum; 7U99; -. DR PDBsum; 7U9A; -. DR PDBsum; 7UKV; -. DR PDBsum; 7UKW; -. DR PDBsum; 7VRA; -. DR PDBsum; 7VRE; -. DR PDBsum; 7ZYM; -. DR PDBsum; 7ZYN; -. DR PDBsum; 7ZYP; -. DR PDBsum; 7ZYQ; -. DR PDBsum; 8A27; -. DR PDBsum; 8A2A; -. DR PDBsum; 8A2B; -. DR PDBsum; 8A2D; -. DR PDBsum; 8D73; -. DR PDBsum; 8D76; -. DR PDBsum; 8DSW; -. DR PDBsum; 8EME; -. DR PDBsum; 8F1H; -. DR PDBsum; 8F1W; -. DR PDBsum; 8F1X; -. DR PDBsum; 8F1Y; -. DR PDBsum; 8F1Z; -. DR PDBsum; 8G63; -. DR PDBsum; 8H7X; -. DR PDBsum; 8HGO; -. DR PDBsum; 8HGP; -. DR PDBsum; 8HGS; -. DR PDBsum; 8HY7; -. DR AlphaFoldDB; P00533; -. DR BMRB; P00533; -. DR EMDB; EMD-25522; -. DR EMDB; EMD-25523; -. DR EMDB; EMD-25558; -. DR EMDB; EMD-25559; -. DR EMDB; EMD-25561; -. DR EMDB; EMD-25563; -. DR EMDB; EMD-34744; -. DR EMDB; EMD-34745; -. DR EMDB; EMD-34746; -. DR SMR; P00533; -. DR BioGRID; 108276; 3125. DR CORUM; P00533; -. DR DIP; DIP-405N; -. DR ELM; P00533; -. DR IntAct; P00533; 838. DR MINT; P00533; -. DR STRING; 9606.ENSP00000275493; -. DR BindingDB; P00533; -. DR ChEMBL; CHEMBL203; -. DR DrugBank; DB15327; Abivertinib. DR DrugBank; DB08916; Afatinib. DR DrugBank; DB03496; Alvocidib. DR DrugBank; DB16695; Amivantamab. DR DrugBank; DB06021; AV-412. DR DrugBank; DB12267; Brigatinib. DR DrugBank; DB05424; Canertinib. DR DrugBank; DB00002; Cetuximab. DR DrugBank; DB11963; Dacomitinib. DR DrugBank; DB11731; Depatuxizumab mafodotin. DR DrugBank; DB00530; Erlotinib. DR DrugBank; DB10772; Foreskin keratinocyte (neonatal). DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB00317; Gefitinib. DR DrugBank; DB11737; Icotinib. DR DrugBank; DB04988; IGN311. DR DrugBank; DB01259; Lapatinib. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB05101; Matuzumab. DR DrugBank; DB16390; Mobocertinib. DR DrugBank; DB09559; Necitumumab. DR DrugBank; DB11828; Neratinib. DR DrugBank; DB13164; Olmutinib. DR DrugBank; DB09330; Osimertinib. DR DrugBank; DB01269; Panitumumab. DR DrugBank; DB07662; PD-168393. DR DrugBank; DB05524; Pelitinib. DR DrugBank; DB12114; Poziotinib. DR DrugBank; DB05374; Rindopepimut. DR DrugBank; DB07602; S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE. DR DrugBank; DB05294; Vandetanib. DR DrugBank; DB05944; Varlitinib. DR DrugBank; DB12202; Zalutumumab. DR DrugBank; DB15035; Zanubrutinib. DR DrugCentral; P00533; -. DR GuidetoPHARMACOLOGY; 1797; -. DR MoonDB; P00533; Predicted. DR TCDB; 8.A.23.1.46; the basigin (basigin) family. DR GlyConnect; 137; 81 N-Linked glycans (10 sites). DR GlyCosmos; P00533; 17 sites, 102 glycans. DR GlyGen; P00533; 23 sites, 101 N-linked glycans (15 sites), 1 O-linked glycan (6 sites). DR iPTMnet; P00533; -. DR MetOSite; P00533; -. DR PhosphoSitePlus; P00533; -. DR SwissPalm; P00533; -. DR BioMuta; EGFR; -. DR DMDM; 2811086; -. DR CPTAC; CPTAC-1043; -. DR CPTAC; CPTAC-1560; -. DR CPTAC; CPTAC-1781; -. DR CPTAC; CPTAC-3043; -. DR CPTAC; CPTAC-3044; -. DR CPTAC; CPTAC-5784; -. DR CPTAC; CPTAC-5785; -. DR CPTAC; CPTAC-5830; -. DR CPTAC; CPTAC-5831; -. DR CPTAC; CPTAC-5832; -. DR CPTAC; CPTAC-5833; -. DR CPTAC; CPTAC-5834; -. DR CPTAC; CPTAC-5835; -. DR CPTAC; CPTAC-802; -. DR CPTAC; non-CPTAC-5380; -. DR CPTAC; non-CPTAC-5381; -. DR CPTAC; non-CPTAC-5382; -. DR CPTAC; non-CPTAC-5545; -. DR CPTAC; non-CPTAC-5546; -. DR CPTAC; non-CPTAC-5735; -. DR CPTAC; non-CPTAC-5736; -. DR CPTAC; non-CPTAC-5737; -. DR CPTAC; non-CPTAC-5738; -. DR EPD; P00533; -. DR jPOST; P00533; -. DR MassIVE; P00533; -. DR MaxQB; P00533; -. DR PaxDb; 9606-ENSP00000275493; -. DR PeptideAtlas; P00533; -. DR ProteomicsDB; 51261; -. [P00533-1] DR ProteomicsDB; 51262; -. [P00533-2] DR ProteomicsDB; 51263; -. [P00533-3] DR ProteomicsDB; 51264; -. [P00533-4] DR ABCD; P00533; 113 sequenced antibodies. DR Antibodypedia; 718; 11977 antibodies from 65 providers. DR CPTC; P00533; 13 antibodies. DR DNASU; 1956; -. DR Ensembl; ENST00000275493.7; ENSP00000275493.2; ENSG00000146648.21. [P00533-1] DR Ensembl; ENST00000342916.7; ENSP00000342376.3; ENSG00000146648.21. [P00533-4] DR Ensembl; ENST00000344576.7; ENSP00000345973.2; ENSG00000146648.21. [P00533-3] DR Ensembl; ENST00000420316.6; ENSP00000413843.2; ENSG00000146648.21. [P00533-2] DR GeneID; 1956; -. DR KEGG; hsa:1956; -. DR MANE-Select; ENST00000275493.7; ENSP00000275493.2; NM_005228.5; NP_005219.2. DR UCSC; uc003tqh.4; human. [P00533-1] DR AGR; HGNC:3236; -. DR CTD; 1956; -. DR DisGeNET; 1956; -. DR GeneCards; EGFR; -. DR HGNC; HGNC:3236; EGFR. DR HPA; ENSG00000146648; Tissue enhanced (placenta). DR MalaCards; EGFR; -. DR MIM; 131550; gene. DR MIM; 211980; phenotype. DR MIM; 616069; phenotype. DR neXtProt; NX_P00533; -. DR OpenTargets; ENSG00000146648; -. DR Orphanet; 251579; Giant cell glioblastoma. DR Orphanet; 251576; Gliosarcoma. DR Orphanet; 294023; Neonatal inflammatory skin and bowel disease. DR PharmGKB; PA7360; -. DR VEuPathDB; HostDB:ENSG00000146648; -. DR eggNOG; KOG1025; Eukaryota. DR GeneTree; ENSGT00940000155450; -. DR HOGENOM; CLU_003384_0_2_1; -. DR InParanoid; P00533; -. DR OMA; KDRYTNC; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P00533; -. DR TreeFam; TF106002; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P00533; -. DR Reactome; R-HSA-1227986; Signaling by ERBB2. DR Reactome; R-HSA-1236382; Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants. DR Reactome; R-HSA-1236394; Signaling by ERBB4. DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling. DR Reactome; R-HSA-1251932; PLCG1 events in ERBB2 signaling. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-177929; Signaling by EGFR. DR Reactome; R-HSA-179812; GRB2 events in EGFR signaling. DR Reactome; R-HSA-180292; GAB1 signalosome. DR Reactome; R-HSA-180336; SHC1 events in EGFR signaling. DR Reactome; R-HSA-182971; EGFR downregulation. DR Reactome; R-HSA-1963640; GRB2 events in ERBB2 signaling. DR Reactome; R-HSA-1963642; PI3K events in ERBB2 signaling. DR Reactome; R-HSA-212718; EGFR interacts with phospholipase C-gamma. DR Reactome; R-HSA-2179392; EGFR Transactivation by Gastrin. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-445144; Signal transduction by L1. DR Reactome; R-HSA-5637810; Constitutive Signaling by EGFRvIII. DR Reactome; R-HSA-5638303; Inhibition of Signaling by Overexpressed EGFR. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6785631; ERBB2 Regulates Cell Motility. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-8847993; ERBB2 Activates PTK6 Signaling. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-8857538; PTK6 promotes HIF1A stabilization. DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling. DR Reactome; R-HSA-8866910; TFAP2 (AP-2) family regulates transcription of growth factors and their receptors. DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling. DR Reactome; R-HSA-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-HSA-9609690; HCMV Early Events. DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling. DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants. DR Reactome; R-HSA-9665348; Signaling by ERBB2 ECD mutants. DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants. DR SignaLink; P00533; -. DR SIGNOR; P00533; -. DR BioGRID-ORCS; 1956; 155 hits in 1222 CRISPR screens. DR ChiTaRS; EGFR; human. DR EvolutionaryTrace; P00533; -. DR GeneWiki; Epidermal_growth_factor_receptor; -. DR GenomeRNAi; 1956; -. DR Pharos; P00533; Tclin. DR PRO; PR:P00533; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P00533; Protein. DR Bgee; ENSG00000146648; Expressed in nipple and 206 other cell types or tissues. DR ExpressionAtlas; P00533; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0009925; C:basal plasma membrane; IBA:GO_Central. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; NAS:UniProtKB. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0097708; C:intracellular vesicle; IDA:ARUK-UCL. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0097489; C:multivesicular body, internal vesicle lumen; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IMP:ARUK-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0032587; C:ruffle membrane; IDA:ARUK-UCL. DR GO; GO:0070435; C:Shc-EGFR complex; ISS:BHF-UCL. DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0051117; F:ATPase binding; ISS:ARUK-UCL. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0005516; F:calmodulin binding; IEA:Ensembl. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; NAS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0048408; F:epidermal growth factor binding; IBA:GO_Central. 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:0005178; F:integrin binding; IEA:Ensembl. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0004709; F:MAP kinase kinase kinase activity; NAS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IDA:MGI. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IEA:Ensembl. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; TAS:Reactome. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW. DR GO; GO:0007202; P:activation of phospholipase C activity; TAS:UniProtKB. DR GO; GO:0048143; P:astrocyte activation; IEA:Ensembl. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI. DR GO; GO:0098609; P:cell-cell adhesion; IMP:UniProtKB. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl. DR GO; GO:0071276; P:cellular response to cadmium ion; IMP:CAFA. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB. DR GO; GO:0071392; P:cellular response to estradiol stimulus; IDA:UniProtKB. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:CAFA. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0021795; P:cerebral cortex cell migration; IEA:Ensembl. DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl. DR GO; GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl. DR GO; GO:0016101; P:diterpenoid metabolic process; IEA:Ensembl. DR GO; GO:0001892; P:embryonic placenta development; IEA:Ensembl. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0038134; P:ERBB2-EGFR signaling pathway; IDA:MGI. DR GO; GO:0061029; P:eyelid development in camera-type eye; IEA:Ensembl. DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl. DR GO; GO:0042743; P:hydrogen peroxide metabolic process; IEA:Ensembl. DR GO; GO:0007611; P:learning or memory; ISS:UniProtKB. DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0007494; P:midgut development; IEA:Ensembl. DR GO; GO:0060571; P:morphogenesis of an epithelial fold; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:1905208; P:negative regulation of cardiocyte differentiation; IMP:BHF-UCL. DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:UniProtKB. DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central. DR GO; GO:0048812; P:neuron projection morphogenesis; IEA:Ensembl. DR GO; GO:0001503; P:ossification; NAS:UniProtKB. DR GO; GO:0042698; P:ovulation cycle; IEA:Ensembl. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IMP:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0045780; P:positive regulation of bone resorption; IEA:Ensembl. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:BHF-UCL. DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI. DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IMP:BHF-UCL. DR GO; GO:0045739; P:positive regulation of DNA repair; IDA:UniProtKB. DR GO; GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:CAFA. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL. DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IMP:BHF-UCL. DR GO; GO:0070257; P:positive regulation of mucus secretion; IEA:Ensembl. DR GO; GO:0010750; P:positive regulation of nitric oxide mediated signal transduction; IDA:UniProtKB. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IMP:CAFA. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:BHF-UCL. DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:UniProtKB. DR GO; GO:1902722; P:positive regulation of prolactin secretion; IEA:Ensembl. DR GO; GO:1900020; P:positive regulation of protein kinase C activity; IDA:ParkinsonsUK-UCL. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IDA:ParkinsonsUK-UCL. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IEA:Ensembl. DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl. DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB. DR GO; GO:0051205; P:protein insertion into membrane; TAS:UniProtKB. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:CAFA. DR GO; GO:0046328; P:regulation of JNK cascade; IMP:CAFA. DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; IDA:UniProtKB. DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IMP:UniProtKB. DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:CAFA. DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl. DR GO; GO:0033590; P:response to cobalamin; IEA:Ensembl. DR GO; GO:0033594; P:response to hydroxyisoflavone; IEA:Ensembl. DR GO; GO:0070141; P:response to UV-A; IDA:BHF-UCL. DR GO; GO:0007435; P:salivary gland morphogenesis; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB. DR GO; GO:0043586; P:tongue development; IEA:Ensembl. DR GO; GO:0006412; P:translation; IEA:Ensembl. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR GO; GO:0042311; P:vasodilation; IEA:Ensembl. DR CDD; cd00064; FU; 3. DR CDD; cd05108; PTKc_EGFR; 1. DR CDD; cd12093; TM_ErbB1; 1. DR Gene3D; 1.20.5.420; Immunoglobulin FC, subunit C; 1. DR Gene3D; 3.80.20.20; Receptor L-domain; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID00262; -. DR InterPro; IPR006211; Furin-like_Cys-rich_dom. DR InterPro; IPR006212; Furin_repeat. DR InterPro; IPR032778; GF_recep_IV. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR000494; Rcpt_L-dom. DR InterPro; IPR036941; Rcpt_L-dom_sf. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR049328; TM_ErbB1. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016245; Tyr_kinase_EGF/ERB/XmrK_rcpt. DR PANTHER; PTHR24416:SF91; EPIDERMAL GROWTH FACTOR RECEPTOR; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF00757; Furin-like; 1. DR Pfam; PF14843; GF_recep_IV; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF01030; Recep_L_domain; 2. DR Pfam; PF21314; TM_ErbB1; 1. DR PIRSF; PIRSF000619; TyrPK_EGF-R; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00261; FU; 3. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 2. DR SUPFAM; SSF52058; L domain-like; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR SWISS-2DPAGE; P00533; -. DR Genevisible; P00533; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Developmental protein; Direct protein sequencing; Disease variant; KW Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; KW Golgi apparatus; Host cell receptor for virus entry; KW Host-virus interaction; Hydroxylation; Isopeptide bond; Kinase; KW Lipoprotein; Membrane; Methylation; Nucleotide-binding; Nucleus; Palmitate; KW Phosphoprotein; Proto-oncogene; Receptor; Reference proteome; Repeat; KW Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; KW Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:15340161, FT ECO:0000269|PubMed:6328312, ECO:0000269|Ref.16" FT CHAIN 25..1210 FT /note="Epidermal growth factor receptor" FT /id="PRO_0000016665" FT TOPO_DOM 25..645 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 646..668 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 669..1210 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 75..300 FT /note="Approximate" FT REPEAT 390..600 FT /note="Approximate" FT DOMAIN 712..979 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 688..704 FT /note="Important for dimerization, phosphorylation and FT activation" FT REGION 1097..1137 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1099..1114 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 837 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 718..726 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:19563760, FT ECO:0007744|PDB:2GS7, ECO:0007744|PDB:3GT8, FT ECO:0007744|PDB:4ZSE, ECO:0007744|PDB:5CNN, FT ECO:0007744|PDB:5CNO, ECO:0007744|PDB:5D41" FT BINDING 745 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:17349580, FT ECO:0000269|PubMed:19563760, ECO:0007744|PDB:2EB3, FT ECO:0007744|PDB:2GS7, ECO:0007744|PDB:2ITN, FT ECO:0007744|PDB:3GT8, ECO:0007744|PDB:3VJN, FT ECO:0007744|PDB:3VJO, ECO:0007744|PDB:4RIW, FT ECO:0007744|PDB:4RIY, ECO:0007744|PDB:4ZSE, FT ECO:0007744|PDB:5CNN, ECO:0007744|PDB:5CNO, FT ECO:0007744|PDB:5D41" FT BINDING 790..791 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:17349580, FT ECO:0000269|PubMed:19563760, ECO:0007744|PDB:2EB3, FT ECO:0007744|PDB:2GS7, ECO:0007744|PDB:2ITN, FT ECO:0007744|PDB:2ITV, ECO:0007744|PDB:2ITX, FT ECO:0007744|PDB:3GT8, ECO:0007744|PDB:3VJN, FT ECO:0007744|PDB:3VJO, ECO:0007744|PDB:4RIW, FT ECO:0007744|PDB:4RIX, ECO:0007744|PDB:4RIY, FT ECO:0007744|PDB:4ZSE, ECO:0007744|PDB:5CNN, FT ECO:0007744|PDB:5CNO, ECO:0007744|PDB:5D41" FT BINDING 855 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:17349580, FT ECO:0000269|PubMed:19563760, ECO:0007744|PDB:2EB3, FT ECO:0007744|PDB:2GS7, ECO:0007744|PDB:2ITN, FT ECO:0007744|PDB:2ITV, ECO:0007744|PDB:2ITX, FT ECO:0007744|PDB:3GT8, ECO:0007744|PDB:3VJN, FT ECO:0007744|PDB:4RIW, ECO:0007744|PDB:4RIX, FT ECO:0007744|PDB:4RIY, ECO:0007744|PDB:4ZSE, FT ECO:0007744|PDB:5CNN, ECO:0007744|PDB:5CNO, FT ECO:0007744|PDB:5D41" FT SITE 1016 FT /note="Important for interaction with PIK3C2B" FT MOD_RES 229 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:21487020" FT MOD_RES 678 FT /note="Phosphothreonine; by PKC and PKD/PRKD1" FT /evidence="ECO:0000269|PubMed:10523301" FT MOD_RES 693 FT /note="Phosphothreonine; by PKD/PRKD1" FT /evidence="ECO:0000269|PubMed:10523301, FT ECO:0000269|PubMed:16083266, ECO:0000269|PubMed:3138233, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 695 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:3138233, FT ECO:0007744|PubMed:18691976" FT MOD_RES 745 FT /note="N6-(2-hydroxyisobutyryl)lysine" FT /evidence="ECO:0000269|PubMed:29192674" FT MOD_RES 869 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:23774213" FT MOD_RES 991 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16083266, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:24275569" FT MOD_RES 995 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 998 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:19563760, FT ECO:0007744|PubMed:18669648" FT MOD_RES 1016 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:19563760, FT ECO:0000269|PubMed:23774213" FT MOD_RES 1026 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16083266, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1039 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1041 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1042 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1064 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1069 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:23774213, FT ECO:0000305|PubMed:22888118" FT MOD_RES 1070 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:3138233" FT MOD_RES 1071 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:3138233" FT MOD_RES 1081 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 1092 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12873986, FT ECO:0000269|PubMed:23774213, ECO:0000269|PubMed:27153536" FT MOD_RES 1110 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12873986, FT ECO:0000269|PubMed:2543678" FT MOD_RES 1166 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:24275569" FT MOD_RES 1172 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:27153536, FT ECO:0007744|PubMed:17081983" FT MOD_RES 1197 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:19563760, FT ECO:0000269|PubMed:19836242, ECO:0000269|PubMed:23774213, FT ECO:0000269|PubMed:27153536, ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231" FT MOD_RES 1199 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000269|PubMed:21258366" FT LIPID 1049 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:27153536" FT LIPID 1146 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:27153536" FT CARBOHYD 56 FT /note="N-linked (GlcNAc...) (complex) asparagine; atypical; FT partial" FT /evidence="ECO:0000269|PubMed:10731668, FT ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, FT ECO:0000269|PubMed:12731890, ECO:0000269|PubMed:16083266, FT ECO:0000269|PubMed:20837704, ECO:0007744|PDB:1IVO, FT ECO:0007744|PDB:1MOX, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ" FT /id="CAR_000227" FT CARBOHYD 73 FT /note="N-linked (GlcNAc...) asparagine; atypical" FT /evidence="ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:3NJP" FT CARBOHYD 128 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12731890, FT ECO:0000269|PubMed:16083266, ECO:0000269|PubMed:8962717" FT CARBOHYD 175 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12297050, FT ECO:0000269|PubMed:12731890, ECO:0000269|PubMed:16083266, FT ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:8962717, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:3NJP" FT CARBOHYD 196 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12731890, FT ECO:0000269|PubMed:16083266, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:3NJP" FT CARBOHYD 352 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:10731668, FT ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, FT ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12731890, FT ECO:0000269|PubMed:16083266, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:20837704, ECO:0007744|PDB:1IVO, FT ECO:0007744|PDB:1MOX, ECO:0007744|PDB:1NQL, FT ECO:0007744|PDB:1YY9, ECO:0007744|PDB:3B2U, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3P0Y, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRL, ECO:0007744|PDB:4KRM, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4KRP, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7" FT CARBOHYD 361 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:10731668, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:12731890, ECO:0000269|PubMed:16083266, FT ECO:0000269|PubMed:20837704, ECO:0007744|PDB:1IVO, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2U, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRL, FT ECO:0007744|PDB:4KRM, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UV7" FT CARBOHYD 413 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12731890, FT ECO:0000269|PubMed:16083266, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:8962717, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2U, ECO:0007744|PDB:3B2V, FT ECO:0007744|PDB:3P0Y, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4KRP" FT CARBOHYD 444 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12297050, FT ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12731890, FT ECO:0000269|PubMed:16083266, ECO:0000269|PubMed:20837704, FT ECO:0000269|PubMed:8962717, ECO:0007744|PDB:1IVO, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2U, ECO:0007744|PDB:3B2V, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3P0Y, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRL, FT ECO:0007744|PDB:4KRM, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7" FT CARBOHYD 528 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:12731890, ECO:0000269|PubMed:16083266, FT ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:25922362, FT ECO:0000269|PubMed:8962717, ECO:0007744|PDB:1NQL, FT ECO:0007744|PDB:1YY9, ECO:0007744|PDB:3B2V, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7" FT CARBOHYD 568 FT /note="N-linked (GlcNAc...) asparagine; partial" FT /evidence="ECO:0000269|PubMed:10731668, FT ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12731890, FT ECO:0000269|PubMed:16083266, ECO:0000269|PubMed:19159218, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9" FT CARBOHYD 603 FT /note="N-linked (GlcNAc...) asparagine; partial" FT /evidence="ECO:0000269|PubMed:10731668, FT ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12731890, FT ECO:0000269|PubMed:16083266, ECO:0007744|PDB:1NQL, FT ECO:0007744|PDB:1YY9" FT CARBOHYD 623 FT /note="N-linked (GlcNAc...) (high mannose) asparagine" FT /evidence="ECO:0000305|PubMed:12731890" FT DISULFID 31..58 FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4KRP, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD" FT DISULFID 157..187 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:5WB7, FT ECO:0007744|PDB:5WB8, ECO:0007744|PDB:5XWD" FT DISULFID 190..199 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5WB7, FT ECO:0007744|PDB:5WB8, ECO:0007744|PDB:5XWD" FT DISULFID 194..207 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5WB7, FT ECO:0007744|PDB:5WB8, ECO:0007744|PDB:5XWD" FT DISULFID 215..223 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD" FT DISULFID 219..231 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD" FT DISULFID 232..240 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4KRP, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD" FT DISULFID 236..248 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4KRP, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD" FT DISULFID 251..260 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4KRP, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD" FT DISULFID 264..291 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5WB7, FT ECO:0007744|PDB:5WB8, ECO:0007744|PDB:5XWD" FT DISULFID 295..307 FT /evidence="ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5WB7, FT ECO:0007744|PDB:5WB8, ECO:0007744|PDB:5XWD" FT DISULFID 311..326 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3G5V, FT ECO:0007744|PDB:3G5Y, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD" FT DISULFID 329..333 FT /evidence="ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5WB7, FT ECO:0007744|PDB:5WB8, ECO:0007744|PDB:5XWD" FT DISULFID 337..362 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2U, ECO:0007744|PDB:3B2V, FT ECO:0007744|PDB:3C09, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3P0Y, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRL, ECO:0007744|PDB:4KRM, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4KRP, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5SX4, ECO:0007744|PDB:5SX5, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD, ECO:0007744|PDB:6B3S" FT DISULFID 470..499 FT /evidence="ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2U, ECO:0007744|PDB:3B2V, FT ECO:0007744|PDB:3C09, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3P0Y, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRL, ECO:0007744|PDB:4KRM, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4KRP, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5SX4, ECO:0007744|PDB:5SX5, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD, ECO:0007744|PDB:6B3S" FT DISULFID 506..515 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2U, ECO:0007744|PDB:3B2V, FT ECO:0007744|PDB:3NJP, ECO:0007744|PDB:3P0Y, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRL, FT ECO:0007744|PDB:4KRM, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5SX4, FT ECO:0007744|PDB:5SX5, ECO:0007744|PDB:5WB7, FT ECO:0007744|PDB:5WB8, ECO:0007744|PDB:5XWD, FT ECO:0007744|PDB:6B3S" FT DISULFID 510..523 FT /evidence="ECO:0000269|PubMed:12297049, FT ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1IVO, ECO:0007744|PDB:1MOX, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2U, ECO:0007744|PDB:3B2V, FT ECO:0007744|PDB:3C09, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3P0Y, ECO:0007744|PDB:3QWQ, FT ECO:0007744|PDB:4KRL, ECO:0007744|PDB:4KRM, FT ECO:0007744|PDB:4KRO, ECO:0007744|PDB:4KRP, FT ECO:0007744|PDB:4UIP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5SX4, ECO:0007744|PDB:5SX5, FT ECO:0007744|PDB:5WB7, ECO:0007744|PDB:5WB8, FT ECO:0007744|PDB:5XWD, ECO:0007744|PDB:6B3S" FT DISULFID 526..535 FT /evidence="ECO:0000269|PubMed:12297050, FT ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:15837620, FT ECO:0000269|PubMed:20837704, ECO:0007744|PDB:1IVO, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRL, FT ECO:0007744|PDB:4KRM, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5XWD" FT DISULFID 539..555 FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5XWD" FT DISULFID 558..571 FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5XWD" FT DISULFID 562..579 FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5XWD" FT DISULFID 582..591 FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UV7, FT ECO:0007744|PDB:5XWD" FT DISULFID 595..617 FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5XWD" FT DISULFID 620..628 FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRO, FT ECO:0007744|PDB:4KRP, ECO:0007744|PDB:4UIP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5XWD" FT DISULFID 624..636 FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:15837620, ECO:0000269|PubMed:20837704, FT ECO:0007744|PDB:1NQL, ECO:0007744|PDB:1YY9, FT ECO:0007744|PDB:3B2V, ECO:0007744|PDB:3NJP, FT ECO:0007744|PDB:3QWQ, ECO:0007744|PDB:4KRP, FT ECO:0007744|PDB:4UV7, ECO:0007744|PDB:5XWD" FT CROSSLNK 716 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:16543144, FT ECO:0000269|PubMed:33996800" FT CROSSLNK 737 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:16543144, FT ECO:0000269|PubMed:33996800" FT CROSSLNK 754 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:16543144, FT ECO:0000269|PubMed:33996800" FT CROSSLNK 757 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:33996800" FT CROSSLNK 867 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:16543144, FT ECO:0000269|PubMed:33996800" FT CROSSLNK 929 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:16543144" FT CROSSLNK 960 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:33996800" FT CROSSLNK 970 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:16543144" FT VAR_SEQ 404..405 FT /note="FL -> LS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7654368, FT ECO:0000303|PubMed:8918811, ECO:0000303|PubMed:9103388, FT ECO:0000303|Ref.6" FT /id="VSP_002887" FT VAR_SEQ 406..1210 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7654368, FT ECO:0000303|PubMed:8918811, ECO:0000303|PubMed:9103388, FT ECO:0000303|Ref.6" FT /id="VSP_002888" FT VAR_SEQ 628..705 FT /note="CTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTL FT RRLLQERELVEPLTPSGEAPNQALLR -> PGNESLKAMLFCLFKLSSCNQSNDGSVSH FT QSGSPAAQESCLGWIPSLLPSEFQLGWGGCSHLHAWPSASVIITASSCH (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:11161793" FT /id="VSP_002889" FT VAR_SEQ 628 FT /note="C -> S (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11161793" FT /id="VSP_002891" FT VAR_SEQ 629..1210 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11161793" FT /id="VSP_002892" FT VAR_SEQ 706..1210 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11161793" FT /id="VSP_002890" FT VARIANT 30..297 FT /note="Missing (variant EGFR vIII; found in a lung cancer FT sample; somatic mutation; induces lung cancer when FT exogenously expressed)" FT /evidence="ECO:0000269|PubMed:16672372" FT /id="VAR_066493" FT VARIANT 98 FT /note="R -> Q (in dbSNP:rs17289589)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_019293" FT VARIANT 266 FT /note="P -> R (in dbSNP:rs17336639)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_019294" FT VARIANT 428 FT /note="G -> D (in NISBD2; loss of function; the mutant does FT not localize to the cell membrane; has diffuse cytoplasmic FT localization; dbSNP:rs606231253)" FT /evidence="ECO:0000269|PubMed:24691054" FT /id="VAR_072435" FT VARIANT 521 FT /note="R -> K (in dbSNP:rs2227983)" FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.7" FT /id="VAR_019295" FT VARIANT 674 FT /note="V -> I (in dbSNP:rs17337079)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_019296" FT VARIANT 709 FT /note="E -> A (found in a lung cancer sample; more FT sensitive to gefitinib than wild-type; dbSNP:rs397517085)" FT /evidence="ECO:0000269|PubMed:15623594, FT ECO:0000269|PubMed:16205628, ECO:0000269|PubMed:16533793" FT /id="VAR_026084" FT VARIANT 709 FT /note="E -> G (found in a lung cancer sample; FT constitutively activated kinase with higher levels of basal FT autophosphorylation; more sensitive to gefitinib than FT wild-type; dbSNP:rs397517085)" FT /evidence="ECO:0000269|PubMed:15623594, FT ECO:0000269|PubMed:16205628" FT /id="VAR_069498" FT VARIANT 709 FT /note="E -> K (found in a lung cancer sample; FT dbSNP:rs727504256)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026085" FT VARIANT 719 FT /note="G -> A (found in a lung cancer sample; FT dbSNP:rs121913428)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026086" FT VARIANT 719 FT /note="G -> C (found in a lung cancer sample; FT dbSNP:rs28929495)" FT /evidence="ECO:0000269|PubMed:15623594, FT ECO:0000269|PubMed:16533793" FT /id="VAR_026087" FT VARIANT 719 FT /note="G -> D (found in a lung cancer sample; FT dbSNP:rs121913428)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026088" FT VARIANT 719 FT /note="G -> S (found in a lung cancer sample; somatic FT mutation; strongly increased kinase activity; FT constitutively activated kinase with higher levels of basal FT autophosphorylation; more sensitive to gefitinib than FT wild-type; dbSNP:rs28929495)" FT /evidence="ECO:0000269|PubMed:15118125, FT ECO:0000269|PubMed:15623594, ECO:0000269|PubMed:16205628, FT ECO:0000269|PubMed:16533793, ECO:0000269|PubMed:17349580" FT /id="VAR_019297" FT VARIANT 724 FT /note="G -> S (found in a lung cancer sample; FT dbSNP:rs1051753269)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026089" FT VARIANT 734 FT /note="E -> K (found in a lung cancer sample; FT dbSNP:rs121913420)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026090" FT VARIANT 746..752 FT /note="ELREATS -> D (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:15623594" FT /id="VAR_069499" FT VARIANT 746..751 FT /note="ELREAT -> A (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:15623594" FT /id="VAR_069500" FT VARIANT 746..750 FT /note="Missing (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:15623594" FT /id="VAR_026092" FT VARIANT 746 FT /note="Missing (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026091" FT VARIANT 747..751 FT /note="Missing (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:15623594" FT /id="VAR_069501" FT VARIANT 747..749 FT /note="Missing (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026094" FT VARIANT 747 FT /note="L -> F (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026093" FT VARIANT 748 FT /note="R -> P (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026095" FT VARIANT 752..759 FT /note="Missing (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026096" FT VARIANT 768 FT /note="S -> I (found in a lung cancer sample; FT constitutively activated kinase with higher levels of basal FT autophosphorylation; more sensitive to gefitinib than FT wild-type; dbSNP:rs121913465)" FT /evidence="ECO:0000269|PubMed:15623594, FT ECO:0000269|PubMed:16205628" FT /id="VAR_069502" FT VARIANT 769 FT /note="V -> M (found in a lung cancer sample; FT dbSNP:rs147149347)" FT /evidence="ECO:0000269|PubMed:15623594" FT /id="VAR_069503" FT VARIANT 787 FT /note="Q -> R (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026097" FT VARIANT 790 FT /note="T -> M (found in a lung cancer sample; increased FT kinase activity; dbSNP:rs121434569)" FT /evidence="ECO:0000269|PubMed:16533793, FT ECO:0000269|PubMed:18227510" FT /id="VAR_026098" FT VARIANT 833 FT /note="L -> V (found in a lung cancer sample; more FT sensitive to gefitinib than wild-type; dbSNP:rs397517126)" FT /evidence="ECO:0000269|PubMed:15623594, FT ECO:0000269|PubMed:16205628, ECO:0000269|PubMed:16533793" FT /id="VAR_026099" FT VARIANT 834 FT /note="V -> L (found in a lung cancer sample; FT dbSNP:rs397517127)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026100" FT VARIANT 835 FT /note="H -> L (found in a lung cancer sample; more FT sensitive to gefitinib than wild-type; dbSNP:rs397517128)" FT /evidence="ECO:0000269|PubMed:15623594, FT ECO:0000269|PubMed:16205628" FT /id="VAR_069504" FT VARIANT 838 FT /note="L -> V (found in a lung cancer sample; more FT sensitive to gefitinib than wild-type; dbSNP:rs864621996)" FT /evidence="ECO:0000269|PubMed:15623594, FT ECO:0000269|PubMed:16205628" FT /id="VAR_069505" FT VARIANT 858 FT /note="L -> M (found in a lung cancer sample; FT dbSNP:rs121913443)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026101" FT VARIANT 858 FT /note="L -> R (found in a lung cancer sample; somatic FT mutation; constitutively activated enzyme with strongly FT increased kinase activity; more sensitive to gefitinib than FT wild-type; dbSNP:rs121434568)" FT /evidence="ECO:0000269|PubMed:15118125, FT ECO:0000269|PubMed:15623594, ECO:0000269|PubMed:16205628, FT ECO:0000269|PubMed:16533793, ECO:0000269|PubMed:17349580" FT /id="VAR_019298" FT VARIANT 861 FT /note="L -> Q (found in a lung cancer sample; FT constitutively activated kinase with higher levels of basal FT autophosphorylation; more sensitive to gefitinib than FT wild-type; dbSNP:rs121913444)" FT /evidence="ECO:0000269|PubMed:15623594, FT ECO:0000269|PubMed:16205628, ECO:0000269|PubMed:16533793" FT /id="VAR_026102" FT VARIANT 873 FT /note="G -> E (found in a lung cancer sample)" FT /evidence="ECO:0000269|PubMed:16533793" FT /id="VAR_026103" FT VARIANT 962 FT /note="R -> G (in dbSNP:rs17337451)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_019299" FT VARIANT 988 FT /note="H -> P (in dbSNP:rs17290699)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_019300" FT VARIANT 1034 FT /note="L -> R (in dbSNP:rs34352568)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042095" FT VARIANT 1210 FT /note="A -> V (in dbSNP:rs35918369)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042096" FT MUTAGEN 275 FT /note="Y->A: Strongly reduced autophosphorylation and FT activation of downstream kinases; when associated with FT A-309." FT /evidence="ECO:0000269|PubMed:12297050" FT MUTAGEN 287 FT /note="F->A: Strongly reduced autophosphorylation and FT activation of downstream kinases; when associated with FT A-309." FT /evidence="ECO:0000269|PubMed:12297050" FT MUTAGEN 309 FT /note="R->S: Strongly reduced autophosphorylation and FT activation of downstream kinases; when associated with FT A-275. Strongly reduced autophosphorylation and activation FT of downstream kinases; when associated with A-287." FT /evidence="ECO:0000269|PubMed:12297050" FT MUTAGEN 429 FT /note="R->E: Abolishes autophosphorylation and activation FT of downstream kinases." FT /evidence="ECO:0000269|PubMed:12297050" FT MUTAGEN 525..1210 FT /note="Missing: Increased EGF binding." FT /evidence="ECO:0000269|PubMed:19718021" FT MUTAGEN 587..590 FT /note="DGPH->AGPA: Decreases intramolecular interactions FT and facilitates EGF binding." FT /evidence="ECO:0000269|PubMed:12620237" FT MUTAGEN 587 FT /note="D->A: Increased EGF binding; when associated with FT A-590 and A-609." FT /evidence="ECO:0000269|PubMed:19718021" FT MUTAGEN 590 FT /note="H->A: Increased EGF binding; when associated with FT A-587; A-590 and A-609." FT /evidence="ECO:0000269|PubMed:19718021" FT MUTAGEN 609 FT /note="K->A: Decreases intramolecular interactions and FT facilitates EGF binding. Increased EGF binding; when FT associated with A-587; A-590 and A-609." FT /evidence="ECO:0000269|PubMed:12620237, FT ECO:0000269|PubMed:19718021" FT MUTAGEN 688 FT /note="L->A: Strongly reduced phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417, FT ECO:0000269|PubMed:19563760" FT MUTAGEN 689 FT /note="V->A: Reduced autophosphorylation." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 689 FT /note="V->M: Constitutively activated kinase." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 690 FT /note="E->A: Reduced phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417, FT ECO:0000269|PubMed:19563760" FT MUTAGEN 692 FT /note="L->A,P: Strongly reduced phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417, FT ECO:0000269|PubMed:19563760" FT MUTAGEN 693 FT /note="T->A: Increased phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 693 FT /note="T->D: Strongly reduced phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 694 FT /note="P->A: Strongly reduced phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 699 FT /note="P->A: Reduced phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 700 FT /note="N->A: Abolishes phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 704 FT /note="L->A: Abolishes phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 705 FT /note="R->A: Abolishes phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 706 FT /note="I->A: Abolishes phosphorylation." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 745 FT /note="K->A,M: Abolishes kinase activity." FT /evidence="ECO:0000269|PubMed:19560417" FT MUTAGEN 974 FT /note="D->A: Strongly reduced phosphorylation." FT MUTAGEN 977 FT /note="R->A: Reduced phosphorylation." FT /evidence="ECO:0000269|PubMed:19563760" FT MUTAGEN 1005..1006 FT /note="ED->RK: Constitutively activated kinase." FT /evidence="ECO:0000269|PubMed:19563760" FT MUTAGEN 1016 FT /note="Y->F: 50% decrease in interaction with PIK3C2B. 65% FT decrease in interaction with PIK3C2B; when associated with FT F-1197. Abolishes interaction with PIK3C2B; when associated FT with F-1197 and F-1092." FT /evidence="ECO:0000269|PubMed:10805725" FT MUTAGEN 1048..1210 FT /note="Missing: Abolishes palmitoylation." FT /evidence="ECO:0000269|PubMed:27153536" FT MUTAGEN 1049 FT /note="C->A: Decreased palmitoylation." FT /evidence="ECO:0000269|PubMed:27153536" FT MUTAGEN 1067 FT /note="Q->G: No effect on interaction with CBLC." FT /evidence="ECO:0000269|PubMed:22888118" FT MUTAGEN 1068 FT /note="R->G: Strongly decreases interaction with CBLC." FT /evidence="ECO:0000269|PubMed:22888118" FT MUTAGEN 1069 FT /note="Y->F: Abolishes interaction with CBLC." FT /evidence="ECO:0000269|PubMed:22888118" FT MUTAGEN 1092 FT /note="Y->F: No change in interaction with PIK3C2B. FT Abolishes interaction with PIK3C2B; when associated with FT F-1197 and F-1016." FT /evidence="ECO:0000269|PubMed:10805725" FT MUTAGEN 1110 FT /note="Y->F: No change in interaction with PIK3C2B." FT /evidence="ECO:0000269|PubMed:10805725" FT MUTAGEN 1146 FT /note="C->A: Decreased palmitoylation." FT /evidence="ECO:0000269|PubMed:27153536" FT MUTAGEN 1172 FT /note="Y->F: No change in interaction with PIK3C2B." FT /evidence="ECO:0000269|PubMed:10805725" FT MUTAGEN 1197 FT /note="Y->F: No change in interaction with PIK3C2B. 65% FT decrease in interaction with PIK3C2B; when associated with FT F-1016. Abolishes interaction with PIK3C2B; when associated FT with F-1092 and F-1016." FT /evidence="ECO:0000269|PubMed:10805725" FT CONFLICT 540 FT /note="N -> K (in Ref. 1; CAA25240)" FT /evidence="ECO:0000305" FT STRAND 40..43 FT /evidence="ECO:0007829|PDB:3QWQ" FT HELIX 44..55 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 60..69 FT /evidence="ECO:0007829|PDB:4UV7" FT HELIX 77..81 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 84..87 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 89..93 FT /evidence="ECO:0007829|PDB:4UV7" FT HELIX 101..103 FT /evidence="ECO:0007829|PDB:1IVO" FT TURN 114..116 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 117..122 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 125..129 FT /evidence="ECO:0007829|PDB:1MOX" FT STRAND 145..152 FT /evidence="ECO:0007829|PDB:4UV7" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:4UV7" FT HELIX 164..166 FT /evidence="ECO:0007829|PDB:4UV7" FT HELIX 170..173 FT /evidence="ECO:0007829|PDB:1MOX" FT STRAND 183..185 FT /evidence="ECO:0007829|PDB:5XWD" FT HELIX 195..197 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 199..204 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 211..214 FT /evidence="ECO:0007829|PDB:1MOX" FT STRAND 217..221 FT /evidence="ECO:0007829|PDB:5XWD" FT STRAND 223..227 FT /evidence="ECO:0007829|PDB:4UV7" FT HELIX 228..230 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 236..238 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 240..244 FT /evidence="ECO:0007829|PDB:4UV7" FT TURN 245..247 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 248..256 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 259..263 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 267..271 FT /evidence="ECO:0007829|PDB:4UV7" FT TURN 272..275 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 276..279 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 285..287 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 290..294 FT /evidence="ECO:0007829|PDB:4UV7" FT TURN 296..298 FT /evidence="ECO:0007829|PDB:3B2V" FT STRAND 299..301 FT /evidence="ECO:0007829|PDB:7LEN" FT STRAND 303..305 FT /evidence="ECO:0007829|PDB:4KRP" FT STRAND 306..310 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 313..315 FT /evidence="ECO:0007829|PDB:3B2V" FT STRAND 318..320 FT /evidence="ECO:0007829|PDB:3G5Y" FT STRAND 323..325 FT /evidence="ECO:0007829|PDB:3G5Y" FT STRAND 330..332 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:3P0Y" FT TURN 340..342 FT /evidence="ECO:0007829|PDB:3QWQ" FT HELIX 343..345 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 349..351 FT /evidence="ECO:0007829|PDB:3P0Y" FT TURN 353..355 FT /evidence="ECO:0007829|PDB:3P0Y" FT HELIX 356..359 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 363..367 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 369..371 FT /evidence="ECO:0007829|PDB:3P0Y" FT HELIX 373..377 FT /evidence="ECO:0007829|PDB:3P0Y" FT TURN 380..383 FT /evidence="ECO:0007829|PDB:3P0Y" FT HELIX 389..397 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 400..403 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 405..407 FT /evidence="ECO:0007829|PDB:3P0Y" FT HELIX 418..420 FT /evidence="ECO:0007829|PDB:3P0Y" FT TURN 433..435 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 436..442 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 458..464 FT /evidence="ECO:0007829|PDB:3P0Y" FT HELIX 472..474 FT /evidence="ECO:0007829|PDB:3P0Y" FT HELIX 477..480 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 481..483 FT /evidence="ECO:0007829|PDB:1YY9" FT STRAND 488..494 FT /evidence="ECO:0007829|PDB:3P0Y" FT HELIX 496..501 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 508..510 FT /evidence="ECO:0007829|PDB:5SX4" FT STRAND 515..519 FT /evidence="ECO:0007829|PDB:3P0Y" FT HELIX 520..522 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 523..526 FT /evidence="ECO:0007829|PDB:3P0Y" FT STRAND 531..533 FT /evidence="ECO:0007829|PDB:4KRL" FT STRAND 535..537 FT /evidence="ECO:0007829|PDB:1YY9" FT STRAND 540..546 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 548..551 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 554..557 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 560..562 FT /evidence="ECO:0007829|PDB:4KRO" FT STRAND 566..568 FT /evidence="ECO:0007829|PDB:1YY9" FT STRAND 570..575 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 578..587 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 590..594 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 597..602 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 606..611 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 615..619 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 622..624 FT /evidence="ECO:0007829|PDB:7SYE" FT STRAND 629..632 FT /evidence="ECO:0007829|PDB:4UV7" FT HELIX 633..635 FT /evidence="ECO:0007829|PDB:4UV7" FT STRAND 643..646 FT /evidence="ECO:0007829|PDB:2KS1" FT HELIX 648..669 FT /evidence="ECO:0007829|PDB:2KS1" FT STRAND 671..673 FT /evidence="ECO:0007829|PDB:1Z9I" FT HELIX 679..684 FT /evidence="ECO:0007829|PDB:3GOP" FT HELIX 685..687 FT /evidence="ECO:0007829|PDB:3GOP" FT STRAND 688..692 FT /evidence="ECO:0007829|PDB:1Z9I" FT STRAND 694..697 FT /evidence="ECO:0007829|PDB:1Z9I" FT STRAND 703..706 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 709..711 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 712..720 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 722..731 FT /evidence="ECO:0007829|PDB:8A27" FT TURN 734..736 FT /evidence="ECO:0007829|PDB:5UG9" FT STRAND 740..749 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 753..767 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 772..774 FT /evidence="ECO:0007829|PDB:6JRJ" FT STRAND 777..781 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 783..785 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 787..791 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 794..797 FT /evidence="ECO:0007829|PDB:5ZWJ" FT HELIX 798..804 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 806..808 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 811..830 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 840..842 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 843..847 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 850..853 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 856..858 FT /evidence="ECO:0007829|PDB:7VRA" FT TURN 859..865 FT /evidence="ECO:0007829|PDB:8A2A" FT HELIX 866..868 FT /evidence="ECO:0007829|PDB:8A2D" FT STRAND 871..873 FT /evidence="ECO:0007829|PDB:6V66" FT STRAND 875..877 FT /evidence="ECO:0007829|PDB:5CZH" FT HELIX 878..880 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 883..888 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 893..908 FT /evidence="ECO:0007829|PDB:8A27" FT TURN 909..911 FT /evidence="ECO:0007829|PDB:7JXW" FT TURN 914..917 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 920..922 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 923..928 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 937..939 FT /evidence="ECO:0007829|PDB:5ZWJ" FT HELIX 941..950 FT /evidence="ECO:0007829|PDB:8A27" FT STRAND 951..953 FT /evidence="ECO:0007829|PDB:5JEB" FT HELIX 955..957 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 961..972 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 975..977 FT /evidence="ECO:0007829|PDB:8A27" FT HELIX 984..986 FT /evidence="ECO:0007829|PDB:5HG8" FT TURN 992..998 FT /evidence="ECO:0007829|PDB:5HG8" FT TURN 999..1003 FT /evidence="ECO:0007829|PDB:6S89" FT STRAND 1004..1010 FT /evidence="ECO:0007829|PDB:3W2S" FT HELIX 1013..1016 FT /evidence="ECO:0007829|PDB:8A2A" FT STRAND 1068..1070 FT /evidence="ECO:0007829|PDB:3PFV" 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 //