Epidermal growth factor receptor

Details

Name
Epidermal growth factor receptor
Synonyms
  • 2.7.10.1
  • ERBB
  • ERBB1
  • HER1
  • Proto-oncogene c-ErbB-1
  • Receptor tyrosine-protein kinase erbB-1
Gene Name
EGFR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001530|Epidermal growth factor receptor MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEV VLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALA VLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGC TGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYV VTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAF ENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKL FGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVM GENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVV ALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGI CLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA RNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPK FRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQ QGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLN TVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRV APQSSEFIGA
Number of residues
1210
分子量
134276.185
Theoretical pI
6.67
GO Classification
Functions
actin filament binding/ATP binding/chromatin binding/double-stranded DNA binding/enzyme binding/epidermal growth factor-activated receptor activity/identical protein binding/MAP kinase kinase kinase activity/protein heterodimerization activity/protein phosphatase binding/蛋白质酪氨酸激酶活性/receptor signaling protein tyrosine kinase activity/transmembrane receptor protein tyrosine kinase activity/transmembrane signaling receptor activity/ubiquitin protein ligase binding
Processes
activation of MAPKK activity/activation of phospholipase A2 activity by calcium-mediated signaling/activation of phospholipase C activity/axon guidance/cell proliferation/cell surface receptor signaling pathway/cellular response to amino acid stimulus/cellular response to epidermal growth factor stimulus/cellular response to estradiol stimulus/cerebral cortex cell migration/digestive tract morphogenesis/embryonic placenta development/epidermal growth factor receptor signaling pathway/Fc-epsilon receptor signaling pathway/fibroblast growth factor receptor signaling pathway/hair follicle development/innate immune response/insulin receptor signaling pathway/learning or memory/MAPK cascade/morphogenesis of an epithelial fold/negative regulation of apoptotic process/negative regulation of epidermal growth factor receptor signaling pathway/negative regulation of protein catabolic process/neurotrophin TRK receptor signaling pathway/ossification/peptidyl-tyrosine phosphorylation/phosphatidylinositol-mediated signaling/positive regulation of catenin import into nucleus/positive regulation of cell migration/positive regulation of cell proliferation/positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle/positive regulation of DNA repair/positive regulation of DNA replication/positive regulation of epithelial cell proliferation/positive regulation of ERK1 and ERK2 cascade/positive regulation of fibroblast proliferation/positive regulation of MAP kinase activity/positive regulation of nitric oxide biosynthetic process/positive regulation of phosphorylation/positive regulation of protein kinase B signaling/positive regulation of protein phosphorylation/positive regulation of transcription from RNA polymerase II promoter/protein autophosphorylation/protein insertion into membrane/Ras protein signal transduction/regulation of nitric-oxide synthase activity/regulation of peptidyl-tyrosine phosphorylation/response to stress/response to UV-A/salivary gland morphogenesis/signal transduction/single organismal cell-cell adhesion/small GTPase mediated signal transduction/vascular endothelial growth factor receptor signaling pathway
Components
basolateral plasma membrane/cell surface/cytoplasm/early endosome membrane/endocytic vesicle/endoplasmic reticulum membrane/endosome/endosome membrane/extracellular space/focal adhesion/Golgi membrane/integral component of membrane/membrane/膜筏/multivesicular body, internal vesicle lumen/nuclear membrane/nucleus/perinuclear region of cytoplasm/plasma membrane/receptor complex/Shc-EGFR complex
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.Isoform 2 may act as an antagonist of EGF action.
Pfam Domain Function
Transmembrane Regions
646-668
Cellular Location
Cell membrane
Gene sequence
>拼箱| BSEQ0019007 |表皮生长因子受体(EGFR) ATGCGACCCTCCGGGACGGCCGGGGCAGCGCTCCTGGCGCTGCTGGCTGCGCTCTGCCCG GCGAGTCGGGCTCTGGAGGAAAAGAAAGTTTGCCAAGGCACGAGTAACAAGCTCACGCAG TTGGGCACTTTTGAAGATCATTTTCTCAGCCTCCAGAGGATGTTCAATAACTGTGAGGTG GTCCTTGGGAATTTGGAAATTACCTATGTGCAGAGGAATTATGATCTTTCCTTCTTAAAG ACCATCCAGGAGGTGGCTGGTTATGTCCTCATTGCCCTCAACACAGTGGAGCGAATTCCT TTGGAAAACCTGCAGATCATCAGAGGAAATATGTACTACGAAAATTCCTATGCCTTAGCA GTCTTATCTAACTATGATGCAAATAAAACCGGACTGAAGGAGCTGCCCATGAGAAATTTA CAGGAAATCCTGCATGGCGCCGTGCGGTTCAGCAACAACCCTGCCCTGTGCAACGTGGAG AGCATCCAGTGGCGGGACATAGTCAGCAGTGACTTTCTCAGCAACATGTCGATGGACTTC CAGAACCACCTGGGCAGCTGCCAAAAGTGTGATCCAAGCTGTCCCAATGGGAGCTGCTGG GGTGCAGGAGAGGAGAACTGCCAGAAACTGACCAAAATCATCTGTGCCCAGCAGTGCTCC GGGCGCTGCCGTGGCAAGTCCCCCAGTGACTGCTGCCACAACCAGTGTGCTGCAGGCTGC ACAGGCCCCCGGGAGAGCGACTGCCTGGTCTGCCGCAAATTCCGAGACGAAGCCACGTGC AAGGACACCTGCCCCCCACTCATGCTCTACAACCCCACCACGTACCAGATGGATGTGAAC CCCGAGGGCAAATACAGCTTTGGTGCCACCTGCGTGAAGAAGTGTCCCCGTAATTATGTG GTGACAGATCACGGCTCGTGCGTCCGAGCCTGTGGGGCCGACAGCTATGAGATGGAGGAA GACGGCGTCCGCAAGTGTAAGAAGTGCGAAGGGCCTTGCCGCAAAGTGTGTAACGGAATA GGTATTGGTGAATTTAAAGACTCACTCTCCATAAATGCTACGAATATTAAACACTTCAAA AACTGCACCTCCATCAGTGGCGATCTCCACATCCTGCCGGTGGCATTTAGGGGTGACTCC TTCACACATACTCCTCCTCTGGATCCACAGGAACTGGATATTCTGAAAACCGTAAAGGAA ATCACAGGGTTTTTGCTGATTCAGGCTTGGCCTGAAAACAGGACGGACCTCCATGCCTTT GAGAACCTAGAAATCATACGCGGCAGGACCAAGCAACATGGTCAGTTTTCTCTTGCAGTC GTCAGCCTGAACATAACATCCTTGGGATTACGCTCCCTCAAGGAGATAAGTGATGGAGAT GTGATAATTTCAGGAAACAAAAATTTGTGCTATGCAAATACAATAAACTGGAAAAAACTG TTTGGGACCTCCGGTCAGAAAACCAAAATTATAAGCAACAGAGGTGAAAACAGCTGCAAG GCCACAGGCCAGGTCTGCCATGCCTTGTGCTCCCCCGAGGGCTGCTGGGGCCCGGAGCCC AGGGACTGCGTCTCTTGCCGGAATGTCAGCCGAGGCAGGGAATGCGTGGACAAGTGCAAC CTTCTGGAGGGTGAGCCAAGGGAGTTTGTGGAGAACTCTGAGTGCATACAGTGCCACCCA GAGTGCCTGCCTCAGGCCATGAACATCACCTGCACAGGACGGGGACCAGACAACTGTATC CAGTGTGCCCACTACATTGACGGCCCCCACTGCGTCAAGACCTGCCCGGCAGGAGTCATG GGAGAAAACAACACCCTGGTCTGGAAGTACGCAGACGCCGGCCATGTGTGCCACCTGTGC CATCCAAACTGCACCTACGGATGCACTGGGCCAGGTCTTGAAGGCTGTCCAACGAATGGG CCTAAGATCCCGTCCATCGCCACTGGGATGGTGGGGGCCCTCCTCTTGCTGCTGGTGGTG GCCCTGGGGATCGGCCTCTTCATGCGAAGGCGCCACATCGTTCGGAAGCGCACGCTGCGG AGGCTGCTGCAGGAGAGGGAGCTTGTGGAGCCTCTTACACCCAGTGGAGAAGCTCCCAAC CAAGCTCTCTTGAGGATCTTGAAGGAAACTGAATTCAAAAAGATCAAAGTGCTGGGCTCC GGTGCGTTCGGCACGGTGTATAAGGGACTCTGGATCCCAGAAGGTGAGAAAGTTAAAATT CCCGTCGCTATCAAGGAATTAAGAGAAGCAACATCTCCGAAAGCCAACAAGGAAATCCTC GATGAAGCCTACGTGATGGCCAGCGTGGACAACCCCCACGTGTGCCGCCTGCTGGGCATC TGCCTCACCTCCACCGTGCAGCTCATCACGCAGCTCATGCCCTTCGGCTGCCTCCTGGAC TATGTCCGGGAACACAAAGACAATATTGGCTCCCAGTACCTGCTCAACTGGTGTGTGCAG ATCGCAAAGGGCATGAACTACTTGGAGGACCGTCGCTTGGTGCACCGCGACCTGGCAGCC AGGAACGTACTGGTGAAAACACCGCAGCATGTCAAGATCACAGATTTTGGGCTGGCCAAA CTGCTGGGTGCGGAAGAGAAAGAATACCATGCAGAAGGAGGCAAAGTGCCTATCAAGTGG ATGGCATTGGAATCAATTTTACACAGAATCTATACCCACCAGAGTGATGTCTGGAGCTAC GGGGTGACCGTTTGGGAGTTGATGACCTTTGGATCCAAGCCATATGACGGAATCCCTGCC AGCGAGATCTCCTCCATCCTGGAGAAAGGAGAACGCCTCCCTCAGCCACCCATATGTACC ATCGATGTCTACATGATCATGGTCAAGTGCTGGATGATAGACGCAGATAGTCGCCCAAAG TTCCGTGAGTTGATCATCGAATTCTCCAAAATGGCCCGAGACCCCCAGCGCTACCTTGTC ATTCAGGGGGATGAAAGAATGCATTTGCCAAGTCCTACAGACTCCAACTTCTACCGTGCC CTGATGGATGAAGAAGACATGGACGACGTGGTGGATGCCGACGAGTACCTCATCCCACAG CAGGGCTTCTTCAGCAGCCCCTCCACGTCACGGACTCCCCTCCTGAGCTCTCTGAGTGCA ACCAGCAACAATTCCACCGTGGCTTGCATTGATAGAAATGGGCTGCAAAGCTGTCCCATC AAGGAAGACAGCTTCTTGCAGCGATACAGCTCAGACCCCACAGGCGCCTTGACTGAGGAC AGCATAGACGACACCTTCCTCCCAGTGCCTGAATACATAAACCAGTCCGTTCCCAAAAGG CCCGCTGGCTCTGTGCAGAATCCTGTCTATCACAATCAGCCTCTGAACCCCGCGCCCAGC AGAGACCCACACTACCAGGACCCCCACAGCACTGCAGTGGGCAACCCCGAGTATCTCAAC ACTGTCCAGCCCACCTGTGTCAACAGCACATTCGACAGCCCTGCCCACTGGGCCCAGAAA GGCAGCCACCAAATTAGCCTGGACAACCCTGACTACCAGCAGGACTTCTTTCCCAAGGAA GCCAAGCCAAATGGCATCTTTAAGGGCTCCACAGCTGAAAATGCAGAATACCTAAGGGTC GCGCCACAAAGCAGTGAATTTATTGGAGCATGA
Chromosome Location
7
Locus
7p12
External Identifiers
Resource Link
UniProtKB ID P00533
UniProtKB Entry Name EGFR_HUMAN
GenBank Protein ID 757924
GenBank Gene ID X00588
GenAtlas ID EGFR
HGNC ID HGNC:3236
General References
  1. Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Libermann TA, Schlessinger J, et al.: Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature. 1984 May 31-Jun 6;309(5967):418-25. [Article]
  2. Ilekis JV, Stark BC, Scoccia B: Possible role of variant RNA transcripts in the regulation of epidermal growth factor receptor expression in human placenta. Mol Reprod Dev. 1995 Jun;41(2):149-56. [Article]
  3. Reiter JL, Maihle NJ: A 1.8 kb alternative transcript from the human epidermal growth factor receptor gene encodes a truncated form of the receptor. Nucleic Acids Res. 1996 Oct 15;24(20):4050-6. [Article]
  4. Ilekis JV, Gariti J, Niederberger C, Scoccia B: Expression of a truncated epidermal growth factor receptor-like protein (TEGFR) in ovarian cancer. Gynecol Oncol. 1997 Apr;65(1):36-41. [Article]
  5. Reiter JL, Threadgill DW, Eley GD, Strunk KE, Danielsen AJ, Sinclair CS, Pearsall RS, Green PJ, Yee D, Lampland AL, Balasubramaniam S, Crossley TD, Magnuson TR, James CD, Maihle NJ: Comparative genomic sequence analysis and isolation of human and mouse alternative EGFR transcripts encoding truncated receptor isoforms. Genomics. 2001 Jan 1;71(1):1-20. [Article]
  6. Lin CR, Chen WS, Kruiger W, Stolarsky LS, Weber W, Evans RM, Verma IM, Gill GN, Rosenfeld MG: Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells. Science. 1984 May 25;224(4651):843-8. [Article]
  7. Xu YH, Ishii S, Clark AJ, Sullivan M, Wilson RK, Ma DP, Roe BA, Merlino GT, Pastan I: Human epidermal growth factor receptor cDNA is homologous to a variety of RNAs overproduced in A431 carcinoma cells. Nature. 1984 Jun 28-Jul 4;309(5971):806-10. [Article]
  8. Simmen FA, Gope ML, Schulz TZ, Wright DA, Carpenter G, O'Malley BW: Isolation of an evolutionarily conserved epidermal growth factor receptor cDNA from human A431 carcinoma cells. Biochem Biophys Res Commun. 1984 Oct 15;124(1):125-32. [Article]
  9. Haley J, Whittle N, Bennet P, Kinchington D, Ullrich A, Waterfield M: The human EGF receptor gene: structure of the 110 kb locus and identification of sequences regulating its transcription. Oncogene Res. 1987 Sep-Oct;1(4):375-96. [Article]
  10. Haley JD, Waterfield MD: Contributory effects of de novo transcription and premature transcript termination in the regulation of human epidermal growth factor receptor proto-oncogene RNA synthesis. J Biol Chem. 1991 Jan 25;266(3):1746-53. [Article]
  11. Ishii S, Xu YH, Stratton RH, Roe BA, Merlino GT, Pastan I: Characterization and sequence of the promoter region of the human epidermal growth factor receptor gene. Proc Natl Acad Sci U S A. 1985 Aug;82(15):4920-4. [Article]
  12. Weber W, Gill GN, Spiess J: Production of an epidermal growth factor receptor-related protein. Science. 1984 Apr 20;224(4646):294-7. [Article]
  13. Heisermann GJ, Gill GN: Epidermal growth factor receptor threonine and serine residues phosphorylated in vivo. J Biol Chem. 1988 Sep 15;263(26):13152-8. [Article]
  14. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. [Article]
  15. Russo MW, Lukas TJ, Cohen S, Staros JV: Identification of residues in the nucleotide binding site of the epidermal growth factor receptor/kinase. J Biol Chem. 1985 May 10;260(9):5205-8. [Article]
  16. Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A: Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. [Article]
  17. Abe Y, Odaka M, Inagaki F, Lax I, Schlessinger J, Kohda D: Disulfide bond structure of human epidermal growth factor receptor. J Biol Chem. 1998 May 1;273(18):11150-7. [Article]
  18. Mroczkowski B, Mosig G, Cohen S: ATP-stimulated interaction between epidermal growth factor receptor and supercoiled DNA. Nature. 1984 May 17-23;309(5965):270-3. [Article]
  19. Carpenter G: Receptors for epidermal growth factor and other polypeptide mitogens. Annu Rev Biochem. 1987;56:881-914. [Article]
  20. Chen WS, Lazar CS, Lund KA, Welsh JB, Chang CP, Walton GM, Der CJ, Wiley HS, Gill GN, Rosenfeld MG: Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation. Cell. 1989 Oct 6;59(1):33-43. [Article]
  21. 马格里斯提单,宽松的我,克里斯R,所作所为M, Honegger AM, Howk R, Givol D, Ullrich A, Schlessinger J: All autophosphorylation sites of epidermal growth factor (EGF) receptor and HER2/neu are located in their carboxyl-terminal tails. Identification of a novel site in EGF receptor. J Biol Chem. 1989 Jun 25;264(18):10667-71. [Article]
  22. Johnson GR, Kannan B, Shoyab M, Stromberg K: Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor and p185erbB2. Evidence that amphiregulin acts exclusively through the epidermal growth factor receptor at the surface of human epithelial cells. J Biol Chem. 1993 Feb 5;268(4):2924-31. [Article]
  23. Galcheva-Gargova Z, Konstantinov KN, Wu IH, Klier FG, Barrett T, Davis RJ: Binding of zinc finger protein ZPR1 to the epidermal growth factor receptor. Science. 1996 Jun 21;272(5269):1797-802. [Article]
  24. Gangwani L, Mikrut M, Galcheva-Gargova Z, Davis RJ: Interaction of ZPR1 with translation elongation factor-1alpha in proliferating cells. J Cell Biol. 1998 Dec 14;143(6):1471-84. [Article]
  25. Bagowski CP, Stein-Gerlach M, Choidas,乌尔里希: Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor. EMBO J. 1999 Oct 15;18(20):5567-76. [Article]
  26. Watanabe T, Shintani A, Nakata M, Shing Y, Folkman J, Igarashi K, Sasada R: Recombinant human betacellulin. Molecular structure, biological activities, and receptor interaction. J Biol Chem. 1994 Apr 1;269(13):9966-73. [Article]
  27. Galisteo ML, Dikic I, Batzer AG, Langdon WY, Schlessinger J: Tyrosine phosphorylation of the c-cbl proto-oncogene protein product and association with epidermal growth factor (EGF) receptor upon EGF stimulation. J Biol Chem. 1995 Sep 1;270(35):20242-5. [Article]
  28. Smith KD, Davies MJ, Bailey D, Renouf DV, Hounsell EF: Analysis of the glycosylation patterns of the extracellular domain of the epidermal growth factor receptor expressed in Chinese hamster ovary fibroblasts. Growth Factors. 1996;13(1-2):121-32. [Article]
  29. Komurasaki T, Toyoda H, Uchida D, Morimoto S: Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. Oncogene. 1997 Dec 4;15(23):2841-8. [Article]
  30. Tiganis T, Bennett AM, Ravichandran KS, Tonks NK: Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase. Mol Cell Biol. 1998 Mar;18(3):1622-34. [Article]
  31. Nesterov A, Carter RE, Sorkina T, Gill GN, Sorkin A: Inhibition of the receptor-binding function of clathrin adaptor protein AP-2 by dominant-negative mutant mu2 subunit and its effects on endocytosis. EMBO J. 1999 May 4;18(9):2489-99. [Article]
  32. Braverman LE, Quilliam LA: Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck. J Biol Chem. 1999 Feb 26;274(9):5542-9. [Article]
  33. Sato C, Kim JH, Abe Y, Saito K, Yokoyama S, Kohda D: Characterization of the N-oligosaccharides attached to the atypical Asn-X-Cys sequence of recombinant human epidermal growth factor receptor. J Biochem. 2000 Jan;127(1):65-72. [Article]
  34. Derrien A, Druey KM: RGS16 function is regulated by epidermal growth factor receptor-mediated tyrosine phosphorylation. J Biol Chem. 2001 Dec 21;276(51):48532-8. Epub 2001 Oct 15. [Article]
  35. Zhen Y, Caprioli RM, Staros JV: Characterization of glycosylation sites of the epidermal growth factor receptor. Biochemistry. 2003 May 13;42(18):5478-92. [Article]
  36. Shao H, Cheng HY, Cook RG, Tweardy DJ: Identification and characterization of signal transducer and activator of transcription 3 recruitment sites within the epidermal growth factor receptor. Cancer Res. 2003 Jul 15;63(14):3923-30. [Article]
  37. Gur G, Rubin C, Katz M, Amit I, Citri A, Nilsson J, Amariglio N, Henriksson R, Rechavi G, Hedman H, Wides R, Yarden Y: LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation. EMBO J. 2004 Aug 18;23(16):3270-81. Epub 2004 Jul 29. [Article]
  38. Arcaro A, Zvelebil MJ, Wallasch C, Ullrich A, Waterfield MD, Domin J: Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors. Mol Cell Biol. 2000 Jun;20(11):3817-30. [Article]
  39. Habib AA, Chatterjee S, Park SK, Ratan RR, Lefebvre S, Vartanian T: The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B. Identification of a novel receptor-tyrosine kinase signalosome. J Biol Chem. 2001 Mar 23;276(12):8865-74. Epub 2000 Dec 14. [Article]
  40. Li Y, Ren J, Yu W, Li Q, Kuwahara H, Yin L, Carraway KL 3rd, Kufe D: The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin. J Biol Chem. 2001 Sep 21;276(38):35239-42. Epub 2001 Aug 1. [Article]
  41. Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y: Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005 Feb 25;280(8):7038-48. Epub 2004 Dec 7. [Article]
  42. Kochupurakkal BS, Harari D, Di-Segni A, Maik-Rachline G, Lyass L, Gur G, Kerber G, Citri A, Lavi S, Eilam R, Chalifa-Caspi V, Eshhar Z, Pikarsky E, Pinkas-Kramarski R, Bacus SS, Yarden Y: Epigen, the last ligand of ErbB receptors, reveals intricate relationships between affinity and mitogenicity. J Biol Chem. 2005 Mar 4;280(9):8503-12. Epub 2004 Dec 17. [Article]
  43. Wu SL, Kim J, Hancock WS, Karger B: Extended Range Proteomic Analysis (ERPA): a new and sensitive LC-MS platform for high sequence coverage of complex proteins with extensive post-translational modifications-comprehensive analysis of beta-casein and epidermal growth factor receptor (EGFR). J Proteome Res. 2005 Jul-Aug;4(4):1155-70. [Article]
  44. Vadlamudi RK, Manavathi B, Balasenthil S, Nair SS, Yang Z, Sahin AA, Kumar R: Functional implications of altered subcellular localization of PELP1 in breast cancer cells. Cancer Res. 2005 Sep 1;65(17):7724-32. [Article]
  45. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [Article]
  46. Wang SC, Nakajima Y, Yu YL, Xia W, Chen CT, Yang CC, McIntush EW, Li LY, Hawke DH, Kobayashi R, Hung MC: Tyrosine phosphorylation controls PCNA function through protein stability. Nat Cell Biol. 2006 Dec;8(12):1359-68. Epub 2006 Nov 19. [Article]
  47. Groenestege WM, Thebault S, van der Wijst J, van den Berg D, Janssen R, Tejpar S, van den Heuvel LP, van Cutsem E, Hoenderop JG, Knoers NV, Bindels RJ: Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J Clin Invest. 2007 Aug;117(8):2260-7. [Article]
  48. Shen F, Lin Q, Gu Y, Childress C, Yang W: Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation. Mol Biol Cell. 2007 Mar;18(3):732-42. Epub 2006 Dec 20. [Article]
  49. Nonis D, Schmidt MH, van de Loo S, Eich F, Dikic I, Nowock J, Auburger G: Ataxin-2 associates with the endocytosis complex and affects EGF receptor trafficking. Cell Signal. 2008 Oct;20(10):1725-39. doi: 10.1016/j.cellsig.2008.05.018. Epub 2008 Jun 15. [Article]
  50. Brummer T, Larance M, Herrera Abreu MT, Lyons RJ, Timpson P, Emmerich CH, Fleuren ED, Lehrbach GM, Schramek D, Guilhaus M, James DE, Daly RJ: Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein. EMBO J. 2008 Sep 3;27(17):2305-16. [Article]
  51. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [Article]
  52. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  53. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  54. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  55. Tarcic G, Boguslavsky SK, Wakim J, Kiuchi T, Liu A, Reinitz F, Nathanson D, Takahashi T, Mischel PS, Ng T, Yarden Y: An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase controlling EGFR endocytosis. Curr Biol. 2009 Nov 17;19(21):1788-98. doi: 10.1016/j.cub.2009.09.048. [Article]
  56. Tashiro K, Tsunematsu T, Okubo H, Ohta T, Sano E, Yamauchi E, Taniguchi H, Konishi H: GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, contributes to cellular transformation through the activation of extracellular signal-regulated kinase signaling. J Biol Chem. 2009 Jul 24;284(30):20206-14. doi: 10.1074/jbc.M109.021139. Epub 2009 Jun 9. [Article]
  57. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [Article]
  58. Oppermann FS, Gnad F,奥尔森的合资企业,公司R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  59. Vivacqua A, Lappano R, De Marco P, Sisci D, Aquila S, De Amicis F, Fuqua SA, Ando S, Maggiolini M: G protein-coupled receptor 30 expression is up-regulated by EGF and TGF alpha in estrogen receptor alpha-positive cancer cells. Mol Endocrinol. 2009 Nov;23(11):1815-26. doi: 10.1210/me.2009-0120. Epub 2009 Sep 11. [Article]
  60. Wang YN, Wang H, Yamaguchi H, Lee HJ, Lee HH, Hung MC: COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport. Biochem Biophys Res Commun. 2010 Sep 3;399(4):498-504. doi: 10.1016/j.bbrc.2010.07.096. Epub 2010 Jul 30. [Article]
  61. Madeo A, Maggiolini M: Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts. Cancer Res. 2010 Jul 15;70(14):6036-46. doi: 10.1158/0008-5472.CAN-10-0408. Epub 2010 Jun 15. [Article]
  62. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  63. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  64. Huang WC, Chen YJ, Li LY, Wei YL, Hsu SC, Tsai SL, Chiu PC, Huang WP, Wang YN, Chen CH, Chang WC, Chang WC, Chen AJ, Tsai CH, Hung MC: Nuclear translocation of epidermal growth factor receptor by Akt-dependent phosphorylation enhances breast cancer-resistant protein expression in gefitinib-resistant cells. J Biol Chem. 2011 Jun 10;286(23):20558-68. doi: 10.1074/jbc.M111.240796. Epub 2011 Apr 12. [Article]
  65. Hsu JM, Chen CT, Chou CK, Kuo HP, Li LY, Lin CY, Lee HJ, Wang YN, Liu M, Liao HW, Shi B, Lai CC, Bedford MT, Tsai CH, Hung MC: Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat Cell Biol. 2011 Feb;13(2):174-81. doi: 10.1038/ncb2158. Epub 2011 Jan 23. [Article]
  66. Guo C, Stark GR: FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-kappaB. Proc Natl Acad Sci U S A. 2011 May 10;108(19):7968-73. doi: 10.1073/pnas.1105369108. Epub 2011 Apr 25. [Article]
  67. Tanno H, Yamaguchi T, Goto E, Ishido S, Komada M: The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane. Mol Biol Cell. 2012 Apr;23(7):1343-53. doi: 10.1091/mbc.E11-09-0817. Epub 2012 Feb 1. [Article]
  68. Pareja F, Ferraro DA, Rubin C, Cohen-Dvashi H, Zhang F, Aulmann S, Ben-Chetrit N, Pines G, Navon R, Crosetto N, Kostler W, Carvalho S, Lavi S, Schmitt F, Dikic I, Yakhini Z, Sinn P, Mills GB, Yarden Y: Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. Oncogene. 2012 Oct 25;31(43):4599-608. doi: 10.1038/onc.2011.587. Epub 2011 Dec 19. [Article]
  69. Smith CJ, Berry DM, McGlade CJ: The E3 ubiquitin ligases RNF126 and Rabring7 regulate endosomal sorting of the epidermal growth factor receptor. J Cell Sci. 2013 Mar 15;126(Pt 6):1366-80. doi: 10.1242/jcs.116129. Epub 2013 Feb 15. [Article]
  70. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  71. Lin X, Zhong S, Ye X, Liao Y, Yao F, Yang X, Sun B, Zhang J, Li Q, Gao Y, Wang Y, Liu J, Han B, Chin YE, Zhou BP, Deng J: EGFR phosphorylates and inhibits lung tumor suppressor GPRC5A in lung cancer. Mol Cancer. 2014 Oct 14;13:233. doi: 10.1186/1476-4598-13-233. [Article]
  72. Cipriano R, Bryson BL, Miskimen KL, Bartel CA, Hernandez-Sanchez W, Bruntz RC, Scott SA, Lindsley CW, Brown HA, Jackson MW: Hyperactivation of EGFR and downstream effector phospholipase D1 by oncogenic FAM83B. Oncogene. 2014 Jun 19;33(25):3298-306. doi: 10.1038/onc.2013.293. Epub 2013 Aug 5. [Article]
  73. Ogiso H, Ishitani R, Nureki O, Fukai S, Yamanaka M, Kim JH, Saito K, Sakamoto A, Inoue M, Shirouzu M, Yokoyama S: Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell. 2002 Sep 20;110(6):775-87. [Article]
  74. Ferguson KM, Berger MB, Mendrola JM, Cho HS, Leahy DJ, Lemmon MA: EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol Cell. 2003 Feb;11(2):507-17. [Article]
  75. Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, Dickerson SH, Ellis B, Pennisi C, Horne E, Lackey K, Alligood KJ, Rusnak DW, Gilmer TM, Shewchuk L: A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res. 2004 Sep 15;64(18):6652-9. [Article]
  76. Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM: Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell. 2005 Apr;7(4):301-11. [Article]
  77. Choowongkomon K, Carlin CR, Sonnichsen FD: A structural model for the membrane-bound form of the juxtamembrane domain of the epidermal growth factor receptor. J Biol Chem. 2005 Jun 24;280(25):24043-52. Epub 2005 Apr 19. [Article]
  78. Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, Eck MJ: Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell. 2007 Mar;11(3):217-27. [Article]
  79. Zhang X, Pickin KA, Bose R, Jura N, Cole PA, Kuriyan J: Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface. Nature. 2007 Nov 29;450(7170):741-4. [Article]
  80. Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ: The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5. doi: 10.1073/pnas.0709662105. Epub 2008 Jan 28. [Article]
  81. Jura N, Endres NF, Engel K, Deindl S, Das R, Lamers MH, Wemmer DE, Zhang X, Kuriyan J: Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment. Cell. 2009 Jun 26;137(7):1293-307. doi: 10.1016/j.cell.2009.04.025. [Article]
  82. 红色啤酒M,崔SH,阿尔瓦拉多D, Moravcevic K, Pozzi A, Lemmon MA, Carpenter G: The juxtamembrane region of the EGF receptor functions as an activation domain. Mol Cell. 2009 Jun 26;34(6):641-51. doi: 10.1016/j.molcel.2009.04.034. [Article]
  83. Mineev KS, Bocharov EV, Pustovalova YE, Bocharova OV, Chupin VV, Arseniev AS: Spatial structure of the transmembrane domain heterodimer of ErbB1 and ErbB2 receptor tyrosine kinases. J Mol Biol. 2010 Jul 9;400(2):231-43. doi: 10.1016/j.jmb.2010.05.016. Epub 2010 May 13. [Article]
  84. Lu C, Mi LZ, Grey MJ, Zhu J, Graef E, Yokoyama S, Springer TA: Structural evidence for loose linkage between ligand binding and kinase activation in the epidermal growth factor receptor. Mol Cell Biol. 2010 Nov;30(22):5432-43. doi: 10.1128/MCB.00742-10. Epub 2010 Sep 13. [Article]
  85. Takeshita K, Tezuka T, Isozaki Y, Yamashita E, Suzuki M, Kim M, Yamanashi Y, Yamamoto T, Nakagawa A: Structural flexibility regulates phosphopeptide-binding activity of the tyrosine kinase binding domain of Cbl-c. J Biochem. 2012 Nov;152(5):487-95. doi: 10.1093/jb/mvs085. Epub 2012 Aug 9. [Article]
  86. 刘黄科幻,惠普,LH, Ku YC,傅YN,蔡HY, Chen YT, Lin YF, Chang WC, Kuo HP, Wu YC, Chen YR, Tsai SF: High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res. 2004 Dec 15;10(24):8195-203. [Article]
  87. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004 Jun 4;304(5676):1497-500. Epub 2004 Apr 29. [Article]
  88. Tam IY, Chung LP, Suen WS, Wang E, Wong MC, Ho KK, Lam WK, Chiu SW, Girard L, Minna JD, Gazdar AF, Wong MP: Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res. 2006 Mar 1;12(5):1647-53. [Article]
  89. Chen YR, Fu YN, Lin CH, Yang ST, Hu SF, Chen YT, Tsai SF, Huang SF: Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants. Oncogene. 2006 Feb 23;25(8):1205-15. [Article]
  90. Ji H, Zhao X, Yuza Y, Shimamura T, Li D, Protopopov A, Jung BL, McNamara K, Xia H, Glatt KA, Thomas RK, Sasaki H, Horner JW, Eck M, Mitchell A, Sun Y, Al-Hashem R, Bronson RT, Rabindran SK, Discafani CM, Maher E, Shapiro GI, Meyerson M, Wong KK: Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7817-22. Epub 2006 May 3. [Article]
  91. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]
  92. Campbell P, Morton PE, Takeichi T, Salam A, Roberts N, Proudfoot LE, Mellerio JE, Aminu K, Wellington C, Patil SN, Akiyama M, Liu L, McMillan JR, Aristodemou S, Ishida-Yamamoto A, Abdul-Wahab A, Petrof G, Fong K, Harnchoowong S, Stone KL, Harper JI, McLean WH, Simpson MA, Parsons M, McGrath JA: Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR. J Invest Dermatol. 2014 Oct;134(10):2570-8. doi: 10.1038/jid.2014.164. Epub 2014 Apr 1. [Article]

Drug Relations

Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details
DB00002 Cetuximab approved yes binder Details
DB00317 Gefitinib 批准,investigational yes antagonist Details
DB00530 Erlotinib 批准,investigational yes antagonist Details
DB01259 Lapatinib 批准,investigational yes antagonist Details
DB01269 Panitumumab 批准,investigational yes suppressor Details
DB00281 Lidocaine approved, vet_approved unknown antagonist Details
DB03496 Alvocidib experimental, investigational unknown Details
DB04988 IGN311 investigational unknown Details
DB05294 Vandetanib approved unknown inhibitor Details
DB05374 Rindopepimut investigational unknown Details
DB05101 Matuzumab investigational unknown Details
DB05424 Canertinib investigational unknown Details
DB05944 Varlitinib investigational unknown Details
DB06021 av - 412 investigational unknown Details
DB05524 Pelitinib investigational unknown Details
DB07602 S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE experimental unknown Details
DB07662 PD-168393 experimental unknown Details
DB08916 Afatinib approved yes inhibitor Details
DB09559 Necitumumab 批准,investigational yes antagonist Details
DB09330 Osimertinib approved yes inhibitorregulator Details
DB11737 Icotinib experimental, investigational unknown antagonist Details
DB13164 Olmutinib investigational yes inhibitor Details
DB12202 Zalutumumab investigational yes antagonist Details
DB11731 Depatuxizumab mafodotin investigational no antibody Details
DB11828 Neratinib 批准,investigational yes inhibitor Details
DB12267 Brigatinib 批准,investigational yes inhibitor Details
DB10772 Foreskin keratinocyte (neonatal) approved yes agonist Details
DB12010 Fostamatinib 批准,investigational unknown inhibitor Details
DB11963 Dacomitinib 批准,investigational yes inhibitor Details
DB15035 Zanubrutinib 批准,investigational unknown inhibitor Details
DB15327 Abivertinib investigational yes inhibitor Details
DB16695 Amivantamab 批准,investigational yes antibodydownregulator Details
DB16390 Mobocertinib 批准,investigational yes inhibitor Details
DB00530 Erlotinib 批准,investigational unknown inhibitor Details
DB12114 Poziotinib investigational unknown inhibitorbinder Details