UniProtKB - P00533 (EGFR_HUMAN)
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>sp|P00533|EGFR_HUMAN Epidermal growth factor receptor OS=Homo sapiens OX=9606 GN=EGFR PE=1 SV=2 MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEV VLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALA VLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGC TGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYV VTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAF ENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKL FGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVM GENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVV ALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGI CLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA RNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPK FRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQ QGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLN TVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRV APQSSEFIGAHelp videoAdd a publicationFeedback
Protein
Epidermal growth factor receptor
Gene
EGFR
Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:
Annotation score:5 out of 5
<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>Select a section on the left to see content.
<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:2790960, PubMed:10805725, PubMed:27153536). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975, PubMed:15611079, PubMed:12297049, PubMed:27153536, PubMed:20837704). 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 (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). 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 (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Plays a role in enhancing learning and memory performance (By similarity).By similarity
<p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More...</a></p> Manual assertion inferred from sequence similarity toi
20 Publications<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More...</a></p> Manual assertion based on experiment ini
- Ref.24"Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation."
Chen W.S., Lazar C.S., Lund K.A., Welsh J.B., Chang C.P., Walton G.M., Der C.J., Wiley H.S., Gill G.N., Rosenfeld M.G.
Cell 59:33-43(1989) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, LIGAND-BINDING. - Ref.26"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."
Johnson G.R., Kannan B., Shoyab M., Stromberg K.
J. Biol. Chem. 268:2924-2931(1993) [PubMed] [Europe PMC] [Abstract]Cited for: IDENTIFICATION OF AREG AS LIGAND, FUNCTION. - Ref.30"Recombinant human betacellulin. Molecular structure, biological activities, and receptor interaction."
Watanabe T., Shintani A., Nakata M., Shing Y., Folkman J., Igarashi K., Sasada R.
J. Biol. Chem. 269:9966-9973(1994) [PubMed] [Europe PMC] [Abstract]Cited for: IDENTIFICATION OF BETACELLULIN/BTC AS LIGAND. - Ref.33"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."
Komurasaki T., Toyoda H., Uchida D., Morimoto S.
Oncogene 15:2841-2848(1997) [PubMed] [Europe PMC] [Abstract]Cited for: IDENTIFICATION OF EPIREGULIN/EREG AS LIGAND, FUNCTION. - Ref.38"RGS16 function is regulated by epidermal growth factor receptor-mediated tyrosine phosphorylation."
Derrien A., Druey K.M.
J. Biol. Chem. 276:48532-48538(2001) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN PHOSPHORYLATION OF RGS16. - Ref.40"Identification and characterization of signal transducer and activator of transcription 3 recruitment sites within the epidermal growth factor receptor."
Shao H., Cheng H.Y., Cook R.G., Tweardy D.J.
Cancer Res. 63:3923-3930(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, INTERACTION WITH STAT3, PHOSPHORYLATION AT TYR-1092 AND TYR-1110. - Ref.42"Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors."
Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D., Domin J.
Mol. Cell. Biol. 20:3817-3830(2000) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN EGFR SIGNALING, IDENTIFICATION IN A COMPLEX WITH PIK3C2A AND ERBB2, IDENTIFICATION IN A COMPLEX WITH PIK3C2B AND ERBB2, INTERACTION WITH PIK3C2B, MUTAGENESIS OF TYR-1016; TYR-1092; TYR-1110; TYR-1172 AND TYR-1197. - Ref.43"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."
Habib A.A., Chatterjee S., Park S.-K., Ratan R.R., Lefebvre S., Vartanian T.
J. Biol. Chem. 276:8865-8874(2001) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN NF-KAPPA-B ACTIVATION, INTERACTION WITH RIPK1. - Ref.44"The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin."
Li Y., Ren J., Yu W., Li Q., Kuwahara H., Yin L., Carraway K.L. III, Kufe D.
J. Biol. Chem. 276:35239-35242(2001) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN PHOSPHORYLATION OF MUC1, INTERACTION WITH MUC1. - Ref.45"Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling."
Kario E., Marmor M.D., Adamsky K., Citri A., Amit I., Amariglio N., Rechavi G., Yarden Y.
J. Biol. Chem. 280:7038-7048(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, ACTIVITY REGULATION, INTERACTION WITH SOCS5. - Ref.46"Epigen, the last ligand of ErbB receptors, reveals intricate relationships between affinity and mitogenicity."
Kochupurakkal B.S., 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 S.S., Yarden Y.
J. Biol. Chem. 280:8503-8512(2005) [PubMed] [Europe PMC] [Abstract]Cited for: IDENTIFICATION OF EPIGEN/EPGN AS A LIGAND, FUNCTION. - Ref.50"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION. - Ref.70"Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation."
Hsu J.M., Chen C.T., Chou C.K., Kuo H.P., Li L.Y., Lin C.Y., Lee H.J., Wang Y.N., Liu M., Liao H.W., Shi B., Lai C.C., Bedford M.T., Tsai C.H., Hung M.C.
Nat. Cell Biol. 13:174-181(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION AND CELL MIGRATION, METHYLATION AT ARG-1199 BY PRMT5, INTERACTION WITH PRMT5 AND PTPN6. - Ref.81"Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling."
Runkle K.B., Kharbanda A., Stypulkowski E., Cao X.J., Wang W., Garcia B.A., Witze E.S.
Mol. Cell 62:385-396(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PALMITOYLATION AT CYS-1049 AND CYS-1146, IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION, PHOSPHORYLATION AT TYR-1092; TYR-1172 AND TYR-1197, SUBCELLULAR LOCATION, MUTAGENESIS OF 1048-ALA--ALA-1210; CYS-1049 AND CYS-1146. - Ref.83"Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha."
Garrett T.P., McKern N.M., Lou M., Elleman T.C., Adams T.E., Lovrecz G.O., Zhu H.J., Walker F., Frenkel M.J., Hoyne P.A., Jorissen R.N., Nice E.C., Burgess A.W., Ward C.W.
Cell 110:763-773(2002) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 25-525 IN COMPLEX WITH TGFA, FUNCTION, GLYCOSYLATION AT ASN-56; ASN-196 AND ASN-352, DISULFIDE BONDS. - Ref.84"Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains."
Ogiso H., Ishitani R., Nureki O., Fukai S., Yamanaka M., Kim J.H., Saito K., Sakamoto A., Inoue M., Shirouzu M., Yokoyama S.
Cell 110:775-787(2002) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 25-646 IN COMPLEX WITH EGF, FUNCTION IN MAPK1 AND/OR MAPK3 ACTIVATION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-275; PHE-287; ARG-309 AND ARG-429, DISULFIDE BONDS, GLYCOSYLATION AT ASN-56; ASN-175; ASN-196; ASN-352; ASN-361 AND ASN-444. - Ref.85"EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization."
Ferguson K.M., Berger M.B., Mendrola J.M., Cho H.S., Leahy D.J., Lemmon M.A.
Mol. Cell 11:507-517(2003) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 25-642 IN COMPLEX WITH EGF, FUNCTION, SUBUNIT, MUTAGENESIS OF 587-ASP--HIS-590 AND LYS-609, DISULFIDE BONDS, GLYCOSYLATION AT ASN-352; ASN-361; ASN-444; ASN-528; ASN-568 AND ASN-603. - Ref.86"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."
Wood E.R., Truesdale A.T., McDonald O.B., Yuan D., Hassell A., Dickerson S.H., Ellis B., Pennisi C., Horne E., Lackey K., Alligood K.J., Rusnak D.W., Gilmer T.M., Shewchuk L.
Cancer Res. 64:6652-6659(2004) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 695-1022 IN COMPLEX WITH GW572016, CATALYTIC ACTIVITY, FUNCTION. - Ref.93"The juxtamembrane region of the EGF receptor functions as an activation domain."
Red Brewer M., Choi S.H., Alvarado D., Moravcevic K., Pozzi A., Lemmon M.A., Carpenter G.
Mol. Cell 34:641-651(2009) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 669-1022 OF MUTANT MET-745, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LEU-688; VAL-689; GLU-690; LEU-692; THR-693; PRO-694; PRO-699; ASN-700; LEU-704; ARG-705; ILE-706 AND LYS-745. - Ref.95"Structural evidence for loose linkage between ligand binding and kinase activation in the epidermal growth factor receptor."
Lu C., Mi L.Z., Grey M.J., Zhu J., Graef E., Yokoyama S., Springer T.A.
Mol. Cell. Biol. 30:5432-5443(2010) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 25-638 IN COMPLEX WITH EGF, FUNCTION, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-56; ASN-73; ASN-175; ASN-196; ASN-352; ASN-361; ASN-444 AND ASN-528.
Isoform 2 may act as an antagonist of EGF action.
(Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins.1 Publication
Manual assertion based on experiment ini
- Ref.71"EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy."
Lupberger J., Zeisel M.B., Xiao F., Thumann C., Fofana I., Zona L., Davis C., Mee C.J., Turek M., Gorke S., Royer C., Fischer B., Zahid M.N., Lavillette D., Fresquet J., Cosset F.L., Rothenberg S.M., Pietschmann T. , Patel A.H., Pessaux P., Doffoel M., Raffelsberger W., Poch O., McKeating J.A., Brino L., Baumert T.F.
Nat. Med. 17:589-595(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION).
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi
- ATPEC:2.7.10.1
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<p>Manual validated information which has been generated by the UniProtKB automatic annotation system.</p> <p><a href="/manual/evidences#ECO:0000255">More...</a></p> Manual assertion according to rulesi
6 PublicationsManual assertion based on experiment ini
- Ref.86"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."
Wood E.R., Truesdale A.T., McDonald O.B., Yuan D., Hassell A., Dickerson S.H., Ellis B., Pennisi C., Horne E., Lackey K., Alligood K.J., Rusnak D.W., Gilmer T.M., Shewchuk L.
Cancer Res. 64:6652-6659(2004) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 695-1022 IN COMPLEX WITH GW572016, CATALYTIC ACTIVITY, FUNCTION. - Ref.89"Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity."
Yun C.H., Boggon T.J., Li Y., Woo M.S., Greulich H., Meyerson M., Eck M.J.
Cancer Cell 11:217-227(2007) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) OF 696-1022 OF WILD-TYPE AND VARIANTS SER-719 AND ARG-858 IN COMPLEXES WITH ATP ANALOGS AND SYNTHETIC INHIBITORS, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, CHARACTERIZATION OF VARIANTS SER-719 AND ARG-858. - Ref.90"Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface."
Zhang X., Pickin K.A., Bose R., Jura N., Cole P.A., Kuriyan J.
Nature 450:741-744(2007) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 702-1022 IN COMPLEX WITH ERRFI1, ACTIVITY REGULATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, INTERACTION WITH ERRFI1. - Ref.91"The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP."
Yun C.H., Mengwasser K.E., Toms A.V., Woo M.S., Greulich H., Wong K.K., Meyerson M., Eck M.J.
Proc. Natl. Acad. Sci. U.S.A. 105:2070-2075(2008) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 695-1022 OF VARIANT MET-790, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT MET-790. - Ref.92"Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment."
Jura N., Endres N.F., Engel K., Deindl S., Das R., Lamers M.H., Wemmer D.E., Zhang X., Kuriyan J.
Cell 137:1293-1307(2009) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF 696-1022, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-998; TYR-1016 AND TYR-1197, MUTAGENESIS OF LEU-688; GLU-690; LEU-692; ARG-977 AND 1005-GLU-ASP-1006, SUBUNIT. - Ref.93"The juxtamembrane region of the EGF receptor functions as an activation domain."
Red Brewer M., Choi S.H., Alvarado D., Moravcevic K., Pozzi A., Lemmon M.A., Carpenter G.
Mol. Cell 34:641-651(2009) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 669-1022 OF MUTANT MET-745, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LEU-688; VAL-689; GLU-690; LEU-692; THR-693; PRO-694; PRO-699; ASN-700; LEU-704; ARG-705; ILE-706 AND LYS-745.
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Manual assertion according to rulesi
6 PublicationsManual assertion based on experiment ini
- Ref.86"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."
Wood E.R., Truesdale A.T., McDonald O.B., Yuan D., Hassell A., Dickerson S.H., Ellis B., Pennisi C., Horne E., Lackey K., Alligood K.J., Rusnak D.W., Gilmer T.M., Shewchuk L.
Cancer Res. 64:6652-6659(2004) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 695-1022 IN COMPLEX WITH GW572016, CATALYTIC ACTIVITY, FUNCTION. - Ref.89"Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity."
Yun C.H., Boggon T.J., Li Y., Woo M.S., Greulich H., Meyerson M., Eck M.J.
Cancer Cell 11:217-227(2007) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) OF 696-1022 OF WILD-TYPE AND VARIANTS SER-719 AND ARG-858 IN COMPLEXES WITH ATP ANALOGS AND SYNTHETIC INHIBITORS, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, CHARACTERIZATION OF VARIANTS SER-719 AND ARG-858. - Ref.90"Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface."
Zhang X., Pickin K.A., Bose R., Jura N., Cole P.A., Kuriyan J.
Nature 450:741-744(2007) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 702-1022 IN COMPLEX WITH ERRFI1, ACTIVITY REGULATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, INTERACTION WITH ERRFI1. - Ref.91"The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP."
Yun C.H., Mengwasser K.E., Toms A.V., Woo M.S., Greulich H., Wong K.K., Meyerson M., Eck M.J.
Proc. Natl. Acad. Sci. U.S.A. 105:2070-2075(2008) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 695-1022 OF VARIANT MET-790, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT MET-790. - Ref.92"Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment."
Jura N., Endres N.F., Engel K., Deindl S., Das R., Lamers M.H., Wemmer D.E., Zhang X., Kuriyan J.
Cell 137:1293-1307(2009) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF 696-1022, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-998; TYR-1016 AND TYR-1197, MUTAGENESIS OF LEU-688; GLU-690; LEU-692; ARG-977 AND 1005-GLU-ASP-1006, SUBUNIT. - Ref.93"The juxtamembrane region of the EGF receptor functions as an activation domain."
Red Brewer M., Choi S.H., Alvarado D., Moravcevic K., Pozzi A., Lemmon M.A., Carpenter G.
Mol. Cell 34:641-651(2009) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 669-1022 OF MUTANT MET-745, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LEU-688; VAL-689; GLU-690; LEU-692; THR-693; PRO-694; PRO-699; ASN-700; LEU-704; ARG-705; ILE-706 AND LYS-745.
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<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi
Endocytosis and inhibition of the activated EGFR by phosphatases like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling.4 Publications
Manual assertion based on experiment ini
- Ref.41"LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation."
Gur G., Rubin C., Katz M., Amit I., Citri A., Nilsson J., Amariglio N., Henriksson R., Rechavi G., Hedman H., Wides R., Yarden Y.
EMBO J. 23:3270-3281(2004) [PubMed] [Europe PMC] [Abstract]Cited for: ACTIVITY REGULATION, INTERACTION WITH LRIG1. - Ref.45"Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling."
Kario E., Marmor M.D., Adamsky K., Citri A., Amit I., Amariglio N., Rechavi G., Yarden Y.
J. Biol. Chem. 280:7038-7048(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, ACTIVITY REGULATION, INTERACTION WITH SOCS5. - Ref.60"An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase controlling EGFR endocytosis."
Tarcic G., Boguslavsky S.K., Wakim J., Kiuchi T., Liu A., Reinitz F., Nathanson D., Takahashi T., Mischel P.S., Ng T., Yarden Y.
Curr. Biol. 19:1788-1798(2009) [PubMed] [Europe PMC] [Abstract]Cited for: ACTIVITY REGULATION BY PTPRJ AND PTPRK, PHOSPHORYLATION AT TYR-1197, DEPHOSPHORYLATION BY PTPRJ, SUBCELLULAR LOCATION, INTERACTION WITH CBL AND GRB2. - Ref.90"Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface."
Zhang X., Pickin K.A., Bose R., Jura N., Cole P.A., Kuriyan J.
Nature 450:741-744(2007) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 702-1022 IN COMPLEX WITH ERRFI1, ACTIVITY REGULATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, INTERACTION WITH ERRFI1.
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei | 745 | ATPCombined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More...</a></p> Manual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| 1 | |
| <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei | 837 | Proton acceptorPROSITE-ProRule annotation Manual assertion according to rulesi | 1 | |
| Binding sitei | 855 | ATPCombined sources Manual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| 1 | |
| <p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei | 1016 | Important for interaction with PIK3C2B | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi | 718 – 726 | ATPCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 9 | |
| Nucleotide bindingi | 790 – 791 | ATPCombined sources Manual assertion inferred from combination of experimental and computational evidencei 2 PublicationsManual assertion based on experiment ini
| 2 |
<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni
- actin filament binding Source: UniProtKB
<p>Inferred from Direct Assay</p>
<p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p>
Inferred from direct assayi
- "Sorting of ligand-activated epidermal growth factor receptor to lysosomes requires its actin-binding domain."
Stoorvogel W., Kerstens S., Fritzsche I., den Hartigh J.C., Oud R., van der Heyden M.A., Voortman J., van Bergen en Henegouwen P.M.
J. Biol. Chem. 279:11562-11569(2004) [PubMed] [Europe PMC] [Abstract]
- ATPase binding Source: ARUK-UCL
- ATP binding Source: UniProtKB-KW
- cadherin binding Source: BHF-UCLInferred from high throughput direct assayi
- "E-cadherin interactome complexity and robustness resolved by quantitative proteomics."
Guo Z., Neilson L.J., Zhong H., Murray P.S., Zanivan S., Zaidel-Bar R.
Sci Signal 7:rs7-rs7(2014) [PubMed] [Europe PMC] [Abstract]
- calmodulin binding Source: Ensembl
- chromatin binding Source: UniProtKBInferred from direct assayi
- Ref.66"Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts."
Madeo A., Maggiolini M.
Cancer Res. 70:6036-6046(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GPER1, SUBCELLULAR LOCATION.
- double-stranded DNA binding Source: UniProtKB
<p>Non-traceable Author Statement</p>
<p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p>
Non-traceable author statementi
- Ref.22"ATP-stimulated interaction between epidermal growth factor receptor and supercoiled DNA."
Mroczkowski B., Mosig G., Cohen S.
Nature 309:270-273(1984) [PubMed] [Europe PMC] [Abstract]Cited for: RECEPTOR ACTIVITY.
- enzyme binding Source: UniProtKB
<p>Inferred from Physical Interaction</p>
<p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p>
Inferred from physical interactioni
- "Plasma membrane phospholipid scramblase 1 is enriched in lipid rafts and interacts with the epidermal growth factor receptor."
Sun J., Nanjundan M., Pike L.J., Wiedmer T., Sims P.J.
Biochemistry 41:6338-6345(2002) [PubMed] [Europe PMC] [Abstract]
- epidermal growth factor-activated receptor activity Source: UniProtKBInferred from direct assayi
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract] - Ref.50"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION.
- epidermal growth factor binding Source: GO_Central
<p>Inferred from Biological aspect of Ancestor</p>
<p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iba">GO evidence code guide</a></p>
Inferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- identical protein binding Source: IntActInferred from physical interactioni
- "An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor."
Zhang X., Gureasko J., Shen K., Cole P.A., Kuriyan J.
Cell 125:1137-1149(2006) [PubMed] [Europe PMC] [Abstract] - "A system for quantifying dynamic protein interactions defines a role for Herceptin in modulating ErbB2 interactions."
Wehrman T.S., Raab W.J., Casipit C.L., Doyonnas R., Pomerantz J.H., Blau H.M.
Proc. Natl. Acad. Sci. U.S.A. 103:19063-19068(2006) [PubMed] [Europe PMC] [Abstract] - "Epidermal growth factor receptor juxtamembrane region regulates allosteric tyrosine kinase activation."
Thiel K.W., Carpenter G.
Proc. Natl. Acad. Sci. U.S.A. 104:19238-19243(2007) [PubMed] [Europe PMC] [Abstract] - Ref.92"Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment."
Jura N., Endres N.F., Engel K., Deindl S., Das R., Lamers M.H., Wemmer D.E., Zhang X., Kuriyan J.
Cell 137:1293-1307(2009) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF 696-1022, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-998; TYR-1016 AND TYR-1197, MUTAGENESIS OF LEU-688; GLU-690; LEU-692; ARG-977 AND 1005-GLU-ASP-1006, SUBUNIT. - "Flow cytometric in situ proximity ligation analyses of protein interactions and post-translational modification of the epidermal growth factor receptor family."
Leuchowius K.J., Weibrecht I., Landegren U., Gedda L., Soderberg O.
Cytometry A 75:833-839(2009) [PubMed] [Europe PMC] [Abstract] - "Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3."
Jura N., Shan Y., Cao X., Shaw D.E., Kuriyan J.
Proc. Natl. Acad. Sci. U.S.A. 106:21608-21613(2009) [PubMed] [Europe PMC] [Abstract] - "Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6."
Deribe Y.L., Wild P., Chandrashaker A., Curak J., Schmidt M.H.H., Kalaidzidis Y., Milutinovic N., Kratchmarova I., Buerkle L., Fetchko M.J., Schmidt P., Kittanakom S., Brown K.R., Jurisica I., Blagoev B., Zerial M., Stagljar I., Dikic I.
Sci Signal 2:ra84-ra84(2009) [PubMed] [Europe PMC] [Abstract] - "A proximity ligation assay using transiently transfected, epitope-tagged proteins: application for in situ detection of dimerized receptor tyrosine kinases."
Gajadhar A., Guha A.
BioTechniques 48:145-152(2010) [PubMed] [Europe PMC] [Abstract] - "PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer."
Serra V., Scaltriti M., Prudkin L., Eichhorn P.J., Ibrahim Y.H., Chandarlapaty S., Markman B., Rodriguez O., Guzman M., Rodriguez S., Gili M., Russillo M., Parra J.L., Singh S., Arribas J., Rosen N., Baselga J.
Oncogene 30:2547-2557(2011) [PubMed] [Europe PMC] [Abstract] - "Comparative analysis of fluorescence resonance energy transfer (FRET) and proximity ligation assay (PLA)."
Mocanu M.M., Varadi T., Szollosi J., Nagy P.
Proteomics 11:2063-2070(2011) [PubMed] [Europe PMC] [Abstract] - "Quantification of receptor tyrosine kinase transactivation through direct dimerization and surface density measurements in single cells."
Swift J.L., Godin A.G., Dore K., Freland L., Bouchard N., Nimmo C., Sergeev M., De Koninck Y., Wiseman P.W., Beaulieu J.M.
Proc. Natl. Acad. Sci. U.S.A. 108:7016-7021(2011) [PubMed] [Europe PMC] [Abstract] - "In situ analysis of mutant EGFRs prevalent in glioblastoma multiforme reveals aberrant dimerization, activation, and differential response to anti-EGFR targeted therapy."
Gajadhar A.S., Bogdanovic E., Munoz D.M., Guha A.
Mol. Cancer Res. 10:428-440(2012) [PubMed] [Europe PMC] [Abstract] - "Oncogenic mutations counteract intrinsic disorder in the EGFR kinase and promote receptor dimerization."
Shan Y., Eastwood M.P., Zhang X., Kim E.T., Arkhipov A., Dror R.O., Jumper J., Kuriyan J., Shaw D.E.
Cell 149:860-870(2012) [PubMed] [Europe PMC] [Abstract] - "Insights into the aberrant activity of mutant EGFR kinase domain and drug recognition."
Gajiwala K.S., Feng J., Ferre R., Ryan K., Brodsky O., Weinrich S., Kath J.C., Stewart A.
Structure 21:209-219(2013) [PubMed] [Europe PMC] [Abstract] - "Conformational coupling across the plasma membrane in activation of the EGF receptor."
Endres N.F., Das R., Smith A.W., Arkhipov A., Kovacs E., Huang Y., Pelton J.G., Shan Y., Shaw D.E., Wemmer D.E., Groves J.T., Kuriyan J.
Cell 152:543-556(2013) [PubMed] [Europe PMC] [Abstract] - "Parallel visualization of multiple protein complexes in individual cells in tumor tissue."
Leuchowius K.J., Clausson C.M., Grannas K., Erbilgin Y., Botling J., Zieba A., Landegren U., Soderberg O.
Mol. Cell Proteomics 12:1563-1571(2013) [PubMed] [Europe PMC] [Abstract] - "EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2."
Shen J., Xia W., Khotskaya Y.B., Huo L., Nakanishi K., Lim S.O., Du Y., Wang Y., Chang W.C., Chen C.H., Hsu J.L., Wu Y., Lam Y.C., James B.P., Liu X., Liu C.G., Patel D.J., Hung M.C.
Nature 497:383-387(2013) [PubMed] [Europe PMC] [Abstract] - "EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in glioblastoma."
Fan Q.W., Cheng C.K., Gustafson W.C., Charron E., Zipper P., Wong R.A., Chen J., Lau J., Knobbe-Thomsen C., Weller M., Jura N., Reifenberger G., Shokat K.M., Weiss W.A.
Cancer Cell 24:438-449(2013) [PubMed] [Europe PMC] [Abstract]
- integrin binding Source: Ensembl
- MAP kinase kinase kinase activity Source: UniProtKBNon-traceable author statementi
- "Activation of the epidermal growth factor receptor by respiratory syncytial virus results in increased inflammation and delayed apoptosis."
Monick M.M., Cameron K., Staber J., Powers L.S., Yarovinsky T.O., Koland J.G., Hunninghake G.W.
J. Biol. Chem. 280:2147-2158(2005) [PubMed] [Europe PMC] [Abstract]
- protein heterodimerization activity Source: UniProtKBInferred from direct assayi
- "Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity."
Fernandes A.M., Hamburger A.W., Gerwin B.I.
Am. J. Respir. Cell Mol. Biol. 21:701-709(1999) [PubMed] [Europe PMC] [Abstract]
- protein kinase binding Source: Ensembl
- protein phosphatase binding Source: UniProtKBInferred from physical interactioni
- "Transforming growth factor {beta} (TGF-{beta})-Smad target gene protein tyrosine phosphatase receptor type kappa is required for TGF-{beta} function."
Wang S.E., Wu F.Y., Shin I., Qu S., Arteaga C.L.
Mol. Cell. Biol. 25:4703-4715(2005) [PubMed] [Europe PMC] [Abstract]
- protein tyrosine kinase activity Source: UniProtKBInferred from direct assayi
- Ref.50"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION. - "The evolutionarily conserved EBR module of RALT/MIG6 mediates suppression of the EGFR catalytic activity."
Anastasi S., Baietti M.F., Frosi Y., Alema S., Segatto O.
Oncogene 26:7833-7846(2007) [PubMed] [Europe PMC] [Abstract]
- transmembrane receptor protein tyrosine kinase activity Source: GO_CentralInferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- transmembrane signaling receptor activity Source: MGIInferred from direct assayi
- "Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation."
Miyazaki T., Liu Z.J., Kawahara A., Minami Y., Yamada K., Tsujimoto Y., Barsoumian E.L., Permutter R.M., Taniguchi T.
Cell 81:223-231(1995) [PubMed] [Europe PMC] [Abstract]
- ubiquitin protein ligase binding Source: UniProtKBInferred from physical interactioni
- Ref.75"The E3 ubiquitin ligases RNF126 and Rabring7 regulate endosomal sorting of the epidermal growth factor receptor."
Smith C.J., Berry D.M., McGlade C.J.
J. Cell Sci. 126:1366-1380(2013) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH RNF115 AND RNF126.
- virus receptor activity Source: UniProtKB-KW
GO - Biological processi
- activation of phospholipase A2 activity by calcium-mediated signaling Source: UniProtKB
<p>Traceable Author Statement</p>
<p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p>
Traceable author statementi
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract]
- activation of phospholipase C activity Source: UniProtKBTraceable author statementi
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract]
- astrocyte activation Source: Ensembl
- cell-cell adhesion Source: UniProtKB
<p>Inferred from Mutant Phenotype</p>
<p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p>
Inferred from mutant phenotypei
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract]
- cell differentiation Source: GO_CentralInferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- cell population proliferation Source: UniProtKBInferred from direct assayi
- Ref.50"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION.
- cell surface receptor signaling pathway Source: MGIInferred from direct assayi
- "Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation."
Miyazaki T., Liu Z.J., Kawahara A., Minami Y., Yamada K., Tsujimoto Y., Barsoumian E.L., Permutter R.M., Taniguchi T.
Cell 81:223-231(1995) [PubMed] [Europe PMC] [Abstract]
- cellular response to amino acid stimulus Source: Ensembl
- cellular response to cadmium ion Source: CAFAInferred from mutant phenotypei
- cellular response to dexamethasone stimulus Source: Ensembl
- cellular response to epidermal growth factor stimulus Source: UniProtKB
- cellular response to estradiol stimulus Source: UniProtKBInferred from direct assayi
- Ref.66"Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts."
Madeo A., Maggiolini M.
Cancer Res. 70:6036-6046(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GPER1, SUBCELLULAR LOCATION.
- cellular response to mechanical stimulus Source: Ensembl
- cellular response to reactive oxygen species Source: CAFAInferred from mutant phenotypei
- cerebral cortex cell migration Source: Ensembl
- circadian rhythm Source: Ensembl
- digestive tract morphogenesis Source: Ensembl
- diterpenoid metabolic process Source: Ensembl
- embryonic placenta development Source: Ensembl
- epidermal growth factor receptor signaling pathway Source: UniProtKBInferred from direct assayi
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract]
- ERBB2 signaling pathway Source: Reactome
- eyelid development in camera-type eye Source: Ensembl
- hair follicle development Source: Ensembl
- hydrogen peroxide metabolic process Source: Ensembl
- learning or memory Source: UniProtKB
- liver regeneration Source: Ensembl
- lung development Source: Ensembl
- magnesium ion homeostasis Source: Ensembl
- MAPK cascade Source: Reactome
- membrane organization Source: Reactome
- midgut development Source: Ensembl
- morphogenesis of an epithelial fold Source: Ensembl
- negative regulation of apoptotic process Source: UniProtKBInferred from mutant phenotypei
- "A novel role of Sprouty 2 in regulating cellular apoptosis."
Edwin F., Patel T.B.
J. Biol. Chem. 283:3181-3190(2008) [PubMed] [Europe PMC] [Abstract]
- negative regulation of cardiocyte differentiation Source: BHF-UCLInferred from mutant phenotypei
- "The promotion of cardiogenic differentiation of hMSCs by targeting epidermal growth factor receptor using microRNA-133a."
Lee S.Y., Ham O., Cha M.J., Song B.W., Choi E., Kim I.K., Chang W., Lim S., Lee C.Y., Park J.H., Lee J., Bae Y., Seo H.H., Choi E., Jang Y., Hwang K.C.
Biomaterials 34:92-99(2013) [PubMed] [Europe PMC] [Abstract]
- negative regulation of epidermal growth factor receptor signaling pathway Source: Reactome
- negative regulation of ERBB signaling pathway Source: Reactome
- negative regulation of mitotic cell cycle Source: Ensembl
- negative regulation of Notch signaling pathway Source: Reactome
- negative regulation of protein catabolic process Source: UniProtKBInferred from direct assayi
- Ref.50"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION.
- neuron projection morphogenesis Source: Ensembl
- ossification Source: UniProtKBNon-traceable author statementi
- "Mice humanised for the EGF receptor display hypomorphic phenotypes in skin, bone and heart."
Sibilia M., Wagner B., Hoebertz A., Elliott C., Marino S., Jochum W., Wagner E.F.
Development 130:4515-4525(2003) [PubMed] [Europe PMC] [Abstract]
- ovulation cycle Source: Ensembl
- peptidyl-tyrosine autophosphorylation Source: UniProtKBInferred from mutant phenotypei
- "Critical involvement of RQCD1 in the EGFR-Akt pathway in mammary carcinogenesis."
Ajiro M., Nishidate T., Katagiri T., Nakamura Y.
Int. J. Oncol. 37:1085-1093(2010) [PubMed] [Europe PMC] [Abstract]
- peptidyl-tyrosine phosphorylation Source: ParkinsonsUK-UCLInferred from direct assayi
- "Diacylglycerol kinase theta counteracts protein kinase C-mediated inactivation of the EGF receptor."
van Baal J., de Widt J., Divecha N., van Blitterswijk W.J.
Int. J. Biochem. Cell Biol. 44:1791-1799(2012) [PubMed] [Europe PMC] [Abstract]
- positive regulation of blood vessel diameter Source: Ensembl
- positive regulation of bone resorption Source: Ensembl
- positive regulation of canonical Wnt signaling pathway Source: BHF-UCLInferred from mutant phenotypei
- "Epidermal growth factor receptor regulates beta-catenin location, stability, and transcriptional activity in oral cancer."
Lee C.H., Hung H.W., Hung P.H., Shieh Y.S.
Mol. Cancer 9:64-64(2010) [PubMed] [Europe PMC] [Abstract]
- positive regulation of cell growth Source: UniProtKBInferred from direct assayi
- "CEACAM1 modulates epidermal growth factor receptor--mediated cell proliferation."
Abou-Rjaily G.A., Lee S.J., May D., Al-Share Q.Y., Deangelis A.M., Ruch R.J., Neumaier M., Kalthoff H., Lin S.H., Najjar S.M.
J. Clin. Invest. 114:944-952(2004) [PubMed] [Europe PMC] [Abstract]
- positive regulation of cell migration Source: UniProtKBInferred from mutant phenotypei
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract] - "Navigator-3, a modulator of cell migration, may act as a suppressor of breast cancer progression."
Cohen-Dvashi H., Ben-Chetrit N., Russell R., Carvalho S., Lauriola M., Nisani S., Mancini M., Nataraj N., Kedmi M., Roth L., Kostler W., Zeisel A., Yitzhaky A., Zylberg J., Tarcic G., Eilam R., Wigelman Y., Will R. , Lavi S., Porat Z., Wiemann S., Ricardo S., Schmitt F., Caldas C., Yarden Y.
EMBO Mol Med 7:299-314(2015) [PubMed] [Europe PMC] [Abstract]
- positive regulation of cell population proliferation Source: MGIInferred from direct assayi
- "Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation."
Miyazaki T., Liu Z.J., Kawahara A., Minami Y., Yamada K., Tsujimoto Y., Barsoumian E.L., Permutter R.M., Taniguchi T.
Cell 81:223-231(1995) [PubMed] [Europe PMC] [Abstract]
- positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCLInferred from mutant phenotypei
- "UVA-induced cell cycle progression is mediated by a disintegrin and metalloprotease/epidermal growth factor receptor/AKT/Cyclin D1 pathways in keratinocytes."
He Y.Y., Council S.E., Feng L., Chignell C.F.
Cancer Res. 68:3752-3758(2008) [PubMed] [Europe PMC] [Abstract]
- positive regulation of DNA repair Source: UniProtKBInferred from direct assayi
- Ref.50"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION.
- positive regulation of DNA replication Source: UniProtKBInferred from direct assayi
- Ref.50"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION.
- positive regulation of epithelial cell proliferation Source: UniProtKBInferred from direct assayi
- "Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity."
Fernandes A.M., Hamburger A.W., Gerwin B.I.
Am. J. Respir. Cell Mol. Biol. 21:701-709(1999) [PubMed] [Europe PMC] [Abstract]
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKBInferred from direct assayi
- Ref.66"Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts."
Madeo A., Maggiolini M.
Cancer Res. 70:6036-6046(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GPER1, SUBCELLULAR LOCATION.
- positive regulation of fibroblast proliferation Source: Ensembl
- positive regulation of G1/S transition of mitotic cell cycle Source: BHF-UCLInferred from mutant phenotypei
- "UVA-induced cell cycle progression is mediated by a disintegrin and metalloprotease/epidermal growth factor receptor/AKT/Cyclin D1 pathways in keratinocytes."
He Y.Y., Council S.E., Feng L., Chignell C.F.
Cancer Res. 68:3752-3758(2008) [PubMed] [Europe PMC] [Abstract]
- positive regulation of inflammatory response Source: Ensembl
- positive regulation of MAP kinase activity Source: UniProtKBInferred from direct assayi
- "Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity."
Fernandes A.M., Hamburger A.W., Gerwin B.I.
Am. J. Respir. Cell Mol. Biol. 21:701-709(1999) [PubMed] [Europe PMC] [Abstract]
- positive regulation of NIK/NF-kappaB signaling Source: CAFAInferred from mutant phenotypei
- positive regulation of nitric oxide mediated signal transduction Source: UniProtKBInferred from direct assayi
- "Activation of epidermal growth factor receptor signals induction of nitric oxide synthase-2 in human optic nerve head astrocytes in glaucomatous optic neuropathy."
Liu B., Neufeld A.H.
Neurobiol. Dis. 13:109-123(2003) [PubMed] [Europe PMC] [Abstract]
- positive regulation of peptidyl-serine phosphorylation Source: UniProtKBInferred from mutant phenotypei
- "Critical involvement of RQCD1 in the EGFR-Akt pathway in mammary carcinogenesis."
Ajiro M., Nishidate T., Katagiri T., Nakamura Y.
Int. J. Oncol. 37:1085-1093(2010) [PubMed] [Europe PMC] [Abstract]
- positive regulation of phosphorylation Source: UniProtKBInferred from direct assayi
- "Epidermal growth factor receptor stimulation activates the RNA binding protein CUG-BP1 and increases expression of C/EBPbeta-LIP in mammary epithelial cells."
Baldwin B.R., Timchenko N.A., Zahnow C.A.
Mol. Cell. Biol. 24:3682-3691(2004) [PubMed] [Europe PMC] [Abstract]
- positive regulation of production of miRNAs involved in gene silencing by miRNA Source: BHF-UCLInferred from mutant phenotypei
- "TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer."
Stinson S., Lackner M.R., Adai A.T., Yu N., Kim H.J., O'Brien C., Spoerke J., Jhunjhunwala S., Boyd Z., Januario T., Newman R.J., Yue P., Bourgon R., Modrusan Z., Stern H.M., Warming S., de Sauvage F.J., Amler L., Yeh R.F., Dornan D.
Sci Signal 4:ra41-ra41(2011) [PubMed] [Europe PMC] [Abstract]
- positive regulation of prolactin secretion Source: Ensembl
- positive regulation of protein kinase B signaling Source: BHF-UCLInferred from mutant phenotypei
- "EGF receptor transactivation and PI3-kinase mediate stimulation of ERK by alpha(2A)-adrenoreceptor in intestinal epithelial cells: a role in wound healing."
Buffin-Meyer B., Crassous P.A., Delage C., Denis C., Schaak S., Paris H.
Eur. J. Pharmacol. 574:85-93(2007) [PubMed] [Europe PMC] [Abstract]
- positive regulation of protein kinase C activity Source: ParkinsonsUK-UCLInferred from direct assayi
- "Diacylglycerol kinase theta counteracts protein kinase C-mediated inactivation of the EGF receptor."
van Baal J., de Widt J., Divecha N., van Blitterswijk W.J.
Int. J. Biochem. Cell Biol. 44:1791-1799(2012) [PubMed] [Europe PMC] [Abstract]
- positive regulation of protein localization to plasma membrane Source: ParkinsonsUK-UCLInferred from direct assayi
- "Diacylglycerol kinase theta counteracts protein kinase C-mediated inactivation of the EGF receptor."
van Baal J., de Widt J., Divecha N., van Blitterswijk W.J.
Int. J. Biochem. Cell Biol. 44:1791-1799(2012) [PubMed] [Europe PMC] [Abstract]
- positive regulation of protein phosphorylation Source: UniProtKBInferred from direct assayi
- Ref.66"Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts."
Madeo A., Maggiolini M.
Cancer Res. 70:6036-6046(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GPER1, SUBCELLULAR LOCATION.
- positive regulation of smooth muscle cell proliferation Source: Ensembl
- positive regulation of superoxide anion generation Source: Ensembl
- positive regulation of synaptic transmission, glutamatergic Source: Ensembl
- positive regulation of transcription, DNA-templated Source: CAFAInferred from mutant phenotypei
- positive regulation of transcription by RNA polymerase II Source: UniProtKBInferred from direct assayi
- Ref.66"Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts."
Madeo A., Maggiolini M.
Cancer Res. 70:6036-6046(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GPER1, SUBCELLULAR LOCATION.
- positive regulation of vasoconstriction Source: Ensembl
- protein autophosphorylation Source: UniProtKBInferred from mutant phenotypei
- "A novel role of Sprouty 2 in regulating cellular apoptosis."
Edwin F., Patel T.B.
J. Biol. Chem. 283:3181-3190(2008) [PubMed] [Europe PMC] [Abstract]
- protein insertion into membrane Source: UniProtKBTraceable author statementi
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract]
- regulation of cell motility Source: Reactome
- regulation of ERK1 and ERK2 cascade Source: CAFAInferred from mutant phenotypei
- regulation of JNK cascade Source: CAFAInferred from mutant phenotypei
- regulation of nitric-oxide synthase activity Source: UniProtKBInferred from direct assayi
- "Activation of epidermal growth factor receptor signals induction of nitric oxide synthase-2 in human optic nerve head astrocytes in glaucomatous optic neuropathy."
Liu B., Neufeld A.H.
Neurobiol. Dis. 13:109-123(2003) [PubMed] [Europe PMC] [Abstract]
- regulation of peptidyl-tyrosine phosphorylation Source: UniProtKBInferred from mutant phenotypei
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract]
- regulation of phosphatidylinositol 3-kinase signaling Source: CAFAInferred from mutant phenotypei
- regulation of transcription by RNA polymerase II Source: Reactome
- response to calcium ion Source: Ensembl
- response to cobalamin Source: Ensembl
- response to hydroxyisoflavone Source: Ensembl
- response to osmotic stress Source: Ensembl
- response to UV-A Source: BHF-UCLInferred from direct assayi
- "UVA-induced cell cycle progression is mediated by a disintegrin and metalloprotease/epidermal growth factor receptor/AKT/Cyclin D1 pathways in keratinocytes."
He Y.Y., Council S.E., Feng L., Chignell C.F.
Cancer Res. 68:3752-3758(2008) [PubMed] [Europe PMC] [Abstract]
- salivary gland morphogenesis Source: Ensembl
- signal transduction Source: UniProtKBInferred from direct assayi
- "Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity."
Fernandes A.M., Hamburger A.W., Gerwin B.I.
Am. J. Respir. Cell Mol. Biol. 21:701-709(1999) [PubMed] [Europe PMC] [Abstract]
- tongue development Source: Ensembl
- translation Source: Ensembl
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_CentralInferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- wound healing Source: Ensembl
<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi
| Molecular function | Developmental protein, Host cell receptor for virus entry, Kinase, Receptor, Transferase, Tyrosine-protein kinase |
| Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDA Comprehensive Enzyme Information System More...BRENDAi | 2.7.10.1 2681 |
Reactome - a knowledgebase of biological pathways and processes More...Reactomei | R-HSA-1227986 Signaling by ERBB2 R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants R-HSA-1236394 Signaling by ERBB4 R-HSA-1250196 SHC1 events in ERBB2 signaling R-HSA-1251932 PLCG1 events in ERBB2 signaling R-HSA-1257604 PIP3 activates AKT signaling R-HSA-177929 Signaling by EGFR R-HSA-179812 GRB2 events in EGFR signaling R-HSA-180292 GAB1 signalosome R-HSA-180336 SHC1 events in EGFR signaling R-HSA-182971 EGFR downregulation R-HSA-1963640 GRB2 events in ERBB2 signaling R-HSA-1963642 PI3K events in ERBB2 signaling R-HSA-212718 EGFR interacts with phospholipase C-gamma R-HSA-2179392 EGFR Transactivation by Gastrin R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-445144 Signal transduction by L1 R-HSA-5637810 Constitutive Signaling by EGFRvIII R-HSA-5638303 Inhibition of Signaling by Overexpressed EGFR R-HSA-5673001 RAF/MAP kinase cascade R-HSA-6785631 ERBB2 Regulates Cell Motility R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-8847993 ERBB2 Activates PTK6 Signaling R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828 Clathrin-mediated endocytosis R-HSA-8857538 PTK6 promotes HIF1A stabilization R-HSA-8863795 Downregulation of ERBB2 signaling R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptors R-HSA-9009391 Extra-nuclear estrogen signaling R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
SignaLink: a signaling pathway resource with multi-layered regulatory networks More...SignaLinki | P00533 |
SIGNOR Signaling Network Open Resource More...SIGNORi | P00533 |
Protein family/group databases
MoonDB Database of extreme multifunctional and moonlighting proteins More...MoonDBi | P00533 Predicted |
<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi | Recommended name: Epidermal growth factor receptor (EC:2.7.10.1
Alternative name(s): Proto-oncogene c-ErbB-1 Receptor tyrosine-protein kinase erbB-1 |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi | Name:EGFR Synonyms:ERBB, ERBB1, HER1 |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>Organismi | Homo sapiens (Human) |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri | 9606 [NCBI] |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineagei | cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi |
|
Organism-specific databases
Human Gene Nomenclature Database More...HGNCi | HGNC:3236 EGFR |
Online Mendelian Inheritance in Man (OMIM) More...MIMi | 131550 gene |
neXtProt; the human protein knowledge platform More...neXtProti | NX_P00533 |
<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi
Nucleus
- Nucleus membrane ; Single-pass type I membrane protein
- Nucleus 3 Publications
Manual assertion based on experiment ini
- Ref.50"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION. - Ref.65"COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport."
Wang Y.N., Wang H., Yamaguchi H., Lee H.J., Lee H.H., Hung M.C.
Biochem. Biophys. Res. Commun. 399:498-504(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH COPG1, SUBCELLULAR LOCATION, TOPOLOGY. - Ref.66"Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts."
Madeo A., Maggiolini M.
Cancer Res. 70:6036-6046(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GPER1, SUBCELLULAR LOCATION.
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication
Manual assertion based on experiment ini
- Ref.81"Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling."
Runkle K.B., Kharbanda A., Stypulkowski E., Cao X.J., Wang W., Garcia B.A., Witze E.S.
Mol. Cell 62:385-396(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PALMITOYLATION AT CYS-1049 AND CYS-1146, IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION, PHOSPHORYLATION AT TYR-1092; TYR-1172 AND TYR-1197, SUBCELLULAR LOCATION, MUTAGENESIS OF 1048-ALA--ALA-1210; CYS-1049 AND CYS-1146.
- Endoplasmic reticulum membrane 1 Publication
Golgi apparatus
Endosome
- Endosome 2 Publications
Manual assertion based on experiment ini
- Ref.53"Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation."
Shen F., Lin Q., Gu Y., Childress C., Yang W.
Mol. Biol. Cell 18:732-742(2007) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TNF2, SUBCELLULAR LOCATION. - Ref.81"Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling."
Runkle K.B., Kharbanda A., Stypulkowski E., Cao X.J., Wang W., Garcia B.A., Witze E.S.
Mol. Cell 62:385-396(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PALMITOYLATION AT CYS-1049 AND CYS-1146, IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION, PHOSPHORYLATION AT TYR-1092; TYR-1172 AND TYR-1197, SUBCELLULAR LOCATION, MUTAGENESIS OF 1048-ALA--ALA-1210; CYS-1049 AND CYS-1146.
- Endosome membrane
- Endosome 2 Publications
Plasma membrane
- Cell membrane 4 Publications
Manual assertion based on experiment ini
- Ref.24"Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation."
Chen W.S., Lazar C.S., Lund K.A., Welsh J.B., Chang C.P., Walton G.M., Der C.J., Wiley H.S., Gill G.N., Rosenfeld M.G.
Cell 59:33-43(1989) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, LIGAND-BINDING. - Ref.53"Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation."
Shen F., Lin Q., Gu Y., Childress C., Yang W.
Mol. Biol. Cell 18:732-742(2007) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TNF2, SUBCELLULAR LOCATION. - Ref.78"Transforming growth factor-beta1 (TGF-beta1)-stimulated fibroblast to myofibroblast differentiation is mediated by hyaluronan (HA)-facilitated epidermal growth factor receptor (EGFR) and CD44 co-localization in lipid rafts."
Midgley A.C., Rogers M., Hallett M.B., Clayton A., Bowen T., Phillips A.O., Steadman R.
J. Biol. Chem. 288:14824-14838(2013) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CD44. - Ref.81"Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling."
Runkle K.B., Kharbanda A., Stypulkowski E., Cao X.J., Wang W., Garcia B.A., Witze E.S.
Mol. Cell 62:385-396(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PALMITOYLATION AT CYS-1049 AND CYS-1146, IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION, PHOSPHORYLATION AT TYR-1092; TYR-1172 AND TYR-1197, SUBCELLULAR LOCATION, MUTAGENESIS OF 1048-ALA--ALA-1210; CYS-1049 AND CYS-1146.
Manual assertion based on experiment ini
- Ref.81"Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling."
Runkle K.B., Kharbanda A., Stypulkowski E., Cao X.J., Wang W., Garcia B.A., Witze E.S.
Mol. Cell 62:385-396(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PALMITOYLATION AT CYS-1049 AND CYS-1146, IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION, PHOSPHORYLATION AT TYR-1092; TYR-1172 AND TYR-1197, SUBCELLULAR LOCATION, MUTAGENESIS OF 1048-ALA--ALA-1210; CYS-1049 AND CYS-1146.
Note: In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER (PubMed:20674546). Endocytosed upon activation by ligand (PubMed:2790960, PubMed:17182860, PubMed:27153536). Colocalized with GPER1 in the nucleus of estrogen agonist-induced cancer-associated fibroblasts (CAF) (PubMed:20551055).4 Publications- Cell membrane 4 Publications
- Ref.24"Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation."
Chen W.S., Lazar C.S., Lund K.A., Welsh J.B., Chang C.P., Walton G.M., Der C.J., Wiley H.S., Gill G.N., Rosenfeld M.G.
Cell 59:33-43(1989) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, LIGAND-BINDING. - Ref.53"Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation."
Shen F., Lin Q., Gu Y., Childress C., Yang W.
Mol. Biol. Cell 18:732-742(2007) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TNF2, SUBCELLULAR LOCATION. - Ref.65"COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport."
Wang Y.N., Wang H., Yamaguchi H., Lee H.J., Lee H.H., Hung M.C.
Biochem. Biophys. Res. Commun. 399:498-504(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH COPG1, SUBCELLULAR LOCATION, TOPOLOGY. - Ref.81"Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling."
Runkle K.B., Kharbanda A., Stypulkowski E., Cao X.J., Wang W., Garcia B.A., Witze E.S.
Mol. Cell 62:385-396(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PALMITOYLATION AT CYS-1049 AND CYS-1146, IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION, PHOSPHORYLATION AT TYR-1092; TYR-1172 AND TYR-1197, SUBCELLULAR LOCATION, MUTAGENESIS OF 1048-ALA--ALA-1210; CYS-1049 AND CYS-1146.
Manual assertion based on experiment ini
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Endosome
- early endosome membrane Source: UniProtKBInferred from direct assayi
- "Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation."
Maleroed L., Stuffers S., Brech A., Stenmark H.
Traffic 8:1617-1629(2007) [PubMed] [Europe PMC] [Abstract]
- endosome Source: UniProtKBInferred from direct assayi
- "Sorting of ligand-activated epidermal growth factor receptor to lysosomes requires its actin-binding domain."
Stoorvogel W., Kerstens S., Fritzsche I., den Hartigh J.C., Oud R., van der Heyden M.A., Voortman J., van Bergen en Henegouwen P.M.
J. Biol. Chem. 279:11562-11569(2004) [PubMed] [Europe PMC] [Abstract] - Ref.53"Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation."
Shen F., Lin Q., Gu Y., Childress C., Yang W.
Mol. Biol. Cell 18:732-742(2007) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TNF2, SUBCELLULAR LOCATION.
- endosome membrane Source: UniProtKBInferred from direct assayi
- "SNX12 role in endosome membrane transport."
Pons V., Ustunel C., Rolland C., Torti E., Parton R.G., Gruenberg J.
PLoS ONE 7:e38949-e38949(2012) [PubMed] [Europe PMC] [Abstract]
- multivesicular body, internal vesicle lumen Source: UniProtKBInferred from direct assayi
- "Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation."
Maleroed L., Stuffers S., Brech A., Stenmark H.
Traffic 8:1617-1629(2007) [PubMed] [Europe PMC] [Abstract]
- early endosome membrane Source: UniProtKBInferred from direct assayi
Extracellular region or secreted
- extracellular space Source: UniProtKBNon-traceable author statementi
- Ref.4"Expression of a truncated epidermal growth factor receptor-like protein (TEGFR) in ovarian cancer."
Ilekis J.V., Gariti J., Niederberger C., Scoccia B.
Gynecol. Oncol. 65:36-41(1997) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
- extracellular space Source: UniProtKBNon-traceable author statementi
Golgi apparatus
- Golgi membrane Source: UniProtKB-SubCell
Nucleus
- nuclear membrane Source: UniProtKB-SubCell
- nucleus Source: UniProtKBInferred from direct assayi
- "Activation of epidermal growth factor receptor signals induction of nitric oxide synthase-2 in human optic nerve head astrocytes in glaucomatous optic neuropathy."
Liu B., Neufeld A.H.
Neurobiol. Dis. 13:109-123(2003) [PubMed] [Europe PMC] [Abstract] - Ref.50"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION. - Ref.66"Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts."
Madeo A., Maggiolini M.
Cancer Res. 70:6036-6046(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GPER1, SUBCELLULAR LOCATION.
Plasma Membrane
- apical plasma membrane Source: Ensembl
- basal plasma membrane Source: GO_CentralInferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- basolateral plasma membrane Source: BHF-UCLInferred from direct assayi
- "Segregation of receptor and ligand regulates activation of epithelial growth factor receptor."
Vermeer P.D., Einwalter L.A., Moninger T.O., Rokhlina T., Kern J.A., Zabner J., Welsh M.J.
Nature 422:322-326(2003) [PubMed] [Europe PMC] [Abstract]
- integral component of plasma membrane Source: GO_CentralInferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- plasma membrane Source: UniProtKBInferred from direct assayi
- Ref.73"The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane."
Tanno H., Yamaguchi T., Goto E., Ishido S., Komada M.
Mol. Biol. Cell 23:1343-1353(2012) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH ANKRD13A; ANKRD13B AND ALKRD13D, UBIQUITINATION, SUBCELLULAR LOCATION.
- Shc-EGFR complex Source: BHF-UCL
Other locations
- cell junction Source: HPA
- cell surface Source: UniProtKBInferred from direct assayi
- "Epidermal growth factor receptor (EGFR) signaling requires a specific endoplasmic reticulum thioredoxin for the post-translational control of receptor presentation to the cell surface."
Dong A., Wodziak D., Lowe A.W.
J. Biol. Chem. 290:8016-8027(2015) [PubMed] [Europe PMC] [Abstract]
- clathrin-coated vesicle membrane Source: Reactome
- cytoplasm Source: UniProtKBInferred from direct assayi
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract] - Ref.73"The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane."
Tanno H., Yamaguchi T., Goto E., Ishido S., Komada M.
Mol. Biol. Cell 23:1343-1353(2012) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH ANKRD13A; ANKRD13B AND ALKRD13D, UBIQUITINATION, SUBCELLULAR LOCATION. - "WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis."
Englert C., Hou X., Maheswaran S., Bennett P., Ngwu C., Re G.G., Garvin A.J., Rosner M.R., Haber D.A.
EMBO J. 14:4662-4675(1995) [PubMed] [Europe PMC] [Abstract]
- endocytic vesicle Source: Ensembl
- focal adhesion Source: UniProtKBInferred from high throughput direct assayi
- "Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for beta-Pix in negative regulation of focal adhesion maturation."
Kuo J.C., Han X., Hsiao C.T., Yates J.R., Waterman C.M.
Nat. Cell Biol. 13:383-393(2011) [PubMed] [Europe PMC] [Abstract]
- membrane Source: UniProtKBInferred from direct assayi
- "Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo."
Andl C.D., Mizushima T., Nakagawa H., Oyama K., Harada H., Chruma K., Herlyn M., Rustgi A.K.
J. Biol. Chem. 278:1824-1830(2003) [PubMed] [Europe PMC] [Abstract]
- membrane raft Source: UniProtKBInferred from direct assayi
- "Plasma membrane phospholipid scramblase 1 is enriched in lipid rafts and interacts with the epidermal growth factor receptor."
Sun J., Nanjundan M., Pike L.J., Wiedmer T., Sims P.J.
Biochemistry 41:6338-6345(2002) [PubMed] [Europe PMC] [Abstract]
- perinuclear region of cytoplasm Source: ARUK-UCLInferred from mutant phenotypei
- protein-containing complex Source: UniProtKBInferred from direct assayi
- "Critical involvement of RQCD1 in the EGFR-Akt pathway in mammary carcinogenesis."
Ajiro M., Nishidate T., Katagiri T., Nakamura Y.
Int. J. Oncol. 37:1085-1093(2010) [PubMed] [Europe PMC] [Abstract]
- receptor complex Source: MGIInferred from direct assayi
- "Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins."
Ghai R., Bugarcic A., Liu H., Norwood S.J., Skeldal S., Coulson E.J., Li S.S., Teasdale R.D., Collins B.M.
Proc. Natl. Acad. Sci. U.S.A. 110:E643-52(2013) [PubMed] [Europe PMC] [Abstract]
- synapse Source: Ensembl
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini | 25 – 645 | ExtracellularSequence analysisAdd BLAST | 621 | |
| <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei | 646 – 668 | HelicalSequence analysisAdd BLAST | 23 | |
| Topological domaini | 669 – 1210 | CytoplasmicSequence analysisAdd BLAST | 542 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Nucleus, Secreted<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi
<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei
Lung cancer (LNCR)3 PublicationsManual assertion based on experiment ini
- Ref.99"EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy."
Paez J.G., Janne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., Herman P., Kaye F.J., Lindeman N., Boggon T.J., Naoki K., Sasaki H., Fujii Y., Eck M.J., Sellers W.R., Johnson B.E., Meyerson M.
Science 304:1497-1500(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS SER-719 AND ARG-858, POSSIBLE INVOLVEMENT IN LUNG CANCER. - Ref.100"Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features."
Tam I.Y.S., Chung L.P., Suen W.S., Wang E., Wong M.C.M., Ho K.K., Lam W.K., Chiu S.W., Girard L., Minna J.D., Gazdar A.F., Wong M.P.
Clin. Cancer Res. 12:1647-1653(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS ALA-709; LYS-709; ALA-719; ASP-719; CYS-719; SER-719; SER-724; LYS-734; GLU-746 DEL; PHE-747; 747-LEU--GLU-749 DEL; PRO-748; 752-SER--ILE-759 DEL; ARG-787; MET-790; VAL-833; LEU-834; MET-858; ARG-858; GLN-861 AND GLU-873, POSSIBLE INVOLVEMENT IN LUNG CANCER. - Ref.102"Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors."
Ji H., Zhao X., Yuza Y., Shimamura T., Li D., Protopopov A., Jung B.L., McNamara K., Xia H., Glatt K.A., Thomas R.K., Sasaki H., Horner J.W., Eck M., Mitchell A., Sun Y., Al-Hashem R., Bronson R.T. , Rabindran S.K., Discafani C.M., Maher E., Shapiro G.I., Meyerson M., Wong K.K.
Proc. Natl. Acad. Sci. U.S.A. 103:7817-7822(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT 30-VAL--ARG-297 DEL, POSSIBLE INVOLVEMENT IN LUNG CANCER.
Ref.99
"EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy."
Paez J.G., Janne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., Herman P., Kaye F.J., Lindeman N., Boggon T.J., Naoki K., Sasaki H., Fujii Y., Eck M.J., Sellers W.R., Johnson B.E., Meyerson M.
Science 304:1497-1500(2004) [PubMed] [Europe PMC] [Abstract]
Paez J.G., Janne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., Herman P., Kaye F.J., Lindeman N., Boggon T.J., Naoki K., Sasaki H., Fujii Y., Eck M.J., Sellers W.R., Johnson B.E., Meyerson M.
Science 304:1497-1500(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SER-719 AND ARG-858, POSSIBLE INVOLVEMENT IN LUNG CANCER.
Ref.100
"Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features."
Tam I.Y.S., Chung L.P., Suen W.S., Wang E., Wong M.C.M., Ho K.K., Lam W.K., Chiu S.W., Girard L., Minna J.D., Gazdar A.F., Wong M.P.
Clin. Cancer Res. 12:1647-1653(2006) [PubMed] [Europe PMC] [Abstract]
Tam I.Y.S., Chung L.P., Suen W.S., Wang E., Wong M.C.M., Ho K.K., Lam W.K., Chiu S.W., Girard L., Minna J.D., Gazdar A.F., Wong M.P.
Clin. Cancer Res. 12:1647-1653(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-709; LYS-709; ALA-719; ASP-719; CYS-719; SER-719; SER-724; LYS-734; GLU-746 DEL; PHE-747; 747-LEU--GLU-749 DEL; PRO-748; 752-SER--ILE-759 DEL; ARG-787; MET-790; VAL-833; LEU-834; MET-858; ARG-858; GLN-861 AND GLU-873, POSSIBLE INVOLVEMENT IN LUNG CANCER.
Ref.102
"Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors."
Ji H., Zhao X., Yuza Y., Shimamura T., Li D., Protopopov A., Jung B.L., McNamara K., Xia H., Glatt K.A., Thomas R.K., Sasaki H., Horner J.W., Eck M., Mitchell A., Sun Y., Al-Hashem R., Bronson R.T. , Rabindran S.K., Discafani C.M., Maher E., Shapiro G.I., Meyerson M., Wong K.K.
Proc. Natl. Acad. Sci. U.S.A. 103:7817-7822(2006) [PubMed] [Europe PMC] [Abstract]
Ji H., Zhao X., Yuza Y., Shimamura T., Li D., Protopopov A., Jung B.L., McNamara K., Xia H., Glatt K.A., Thomas R.K., Sasaki H., Horner J.W., Eck M., Mitchell A., Sun Y., Al-Hashem R., Bronson R.T. , Rabindran S.K., Discafani C.M., Maher E., Shapiro G.I., Meyerson M., Wong K.K.
Proc. Natl. Acad. Sci. U.S.A. 103:7817-7822(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT 30-VAL--ARG-297 DEL, POSSIBLE INVOLVEMENT IN LUNG CANCER.
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionA common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.
Related information in OMIMInflammatory skin and bowel disease, neonatal, 2 (NISBD2)1 PublicationManual assertion based on experiment ini
- Ref.104"Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR."
Campbell P., Morton P.E., Takeichi T., Salam A., Roberts N., Proudfoot L.E., Mellerio J.E., Aminu K., Wellington C., Patil S.N., Akiyama M., Liu L., McMillan J.R., Aristodemou S., Ishida-Yamamoto A., Abdul-Wahab A., Petrof G., Fong K. , Harnchoowong S., Stone K.L., Harper J.I., McLean W.H., Simpson M.A., Parsons M., McGrath J.A.
J. Invest. Dermatol. 134:2570-2578(2014) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NISBD2 ASP-428, CHARACTERIZATION OF VARIANT NISBD2 ASP-428, INVOLVEMENT IN NISBD2.
Ref.104
"Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR."
Campbell P., Morton P.E., Takeichi T., Salam A., Roberts N., Proudfoot L.E., Mellerio J.E., Aminu K., Wellington C., Patil S.N., Akiyama M., Liu L., McMillan J.R., Aristodemou S., Ishida-Yamamoto A., Abdul-Wahab A., Petrof G., Fong K. , Harnchoowong S., Stone K.L., Harper J.I., McLean W.H., Simpson M.A., Parsons M., McGrath J.A.
J. Invest. Dermatol. 134:2570-2578(2014) [PubMed] [Europe PMC] [Abstract]
Campbell P., Morton P.E., Takeichi T., Salam A., Roberts N., Proudfoot L.E., Mellerio J.E., Aminu K., Wellington C., Patil S.N., Akiyama M., Liu L., McMillan J.R., Aristodemou S., Ishida-Yamamoto A., Abdul-Wahab A., Petrof G., Fong K. , Harnchoowong S., Stone K.L., Harper J.I., McLean W.H., Simpson M.A., Parsons M., McGrath J.A.
J. Invest. Dermatol. 134:2570-2578(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NISBD2 ASP-428, CHARACTERIZATION OF VARIANT NISBD2 ASP-428, INVOLVEMENT IN NISBD2.
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_072435 | 428 | G → D in NISBD2; loss of function; the mutant does not localize to the cell membrane; has diffuse cytoplasmic localization. 1 Publication Manual assertion based on experiment ini
| 1 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi | 275 | Y → A: Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-309. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 287 | F → A: Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-309. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 309 | R → S: Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-275. Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-287. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 429 | R → E: Abolishes autophosphorylation and activation of downstream kinases. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 587 – 590 | DGPH → AGPA: Decreases intramolecular interactions and facilitates EGF binding. 1 Publication Manual assertion based on experiment ini
| 4 | |
| Mutagenesisi | 609 | K → A: Decreases intramolecular interactions and facilitates EGF binding. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 688 | L → A: Strongly reduced phosphorylation. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 689 | V → A: Reduced autophosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 689 | V → M: Constitutively activated kinase. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 690 | E → A: Reduced phosphorylation. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 692 | L → A or P: Strongly reduced phosphorylation. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 693 | T → A: Increased phosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 693 | T → D: Strongly reduced phosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 694 | P → A: Strongly reduced phosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 699 | P → A: Reduced phosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 700 | N → A: Abolishes phosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 704 | L → A: Abolishes phosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 705 | R → A: Abolishes phosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 706 | I → A: Abolishes phosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 745 | K → A or M: Abolishes kinase activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 974 | D → A: Strongly reduced phosphorylation. | 1 | |
| Mutagenesisi | 977 | R → A: Reduced phosphorylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1005 – 1006 | ED → RK: Constitutively activated kinase. 1 Publication Manual assertion based on experiment ini
| 2 | |
| Mutagenesisi | 1016 | Y → F: 50% decrease in interaction with PIK3C2B. 65% decrease in interaction with PIK3C2B; when associated with F-1197. Abolishes interaction with PIK3C2B; when associated with F-1197 and F-1092. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1048 – 1210 | Missing : Abolishes palmitoylation. 1 Publication Manual assertion based on experiment ini
| 163 | |
| Mutagenesisi | 1049 | C → A: Decreased palmitoylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1067 | Q → G: No effect on interaction with CBLC. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1068 | R → G: Strongly decreases interaction with CBLC. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1069 | Y → F: Abolishes interaction with CBLC. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1092 | Y → F: No change in interaction with PIK3C2B. Abolishes interaction with PIK3C2B; when associated with F-1197 and F-1016. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1110 | Y → F: No change in interaction with PIK3C2B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1146 | C → A: Decreased palmitoylation. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1172 | Y → F: No change in interaction with PIK3C2B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 1197 | Y → F: No change in interaction with PIK3C2B. 65% decrease in interaction with PIK3C2B; when associated with F-1016. Abolishes interaction with PIK3C2B; when associated with F-1092 and F-1016. 1 Publication Manual assertion based on experiment ini
| 1 |
Keywords - Diseasei
Disease mutation, Proto-oncogeneOrganism-specific databases
DisGeNET More...DisGeNETi | 1956 |
MalaCards human disease database More...MalaCardsi | EGFR |
| MIMi | 211980 phenotype 616069 phenotype |
Open Targets More...OpenTargetsi | ENSG00000146648 |
Orphanet; a database dedicated to information on rare diseases and orphan drugs More...Orphaneti | 251579 Giant cell glioblastoma 251576 Gliosarcoma 294023 Neonatal inflammatory skin and bowel disease 357191 Selection of therapeutic option in non-small cell lung carcinoma |
The Pharmacogenetics and Pharmacogenomics Knowledge Base More...PharmGKBi | PA7360 |
Miscellaneous databases
Pharos NIH Druggable Genome Knowledgebase More...Pharosi | P00533 |
Chemistry databases
ChEMBL database of bioactive drug-like small molecules More...ChEMBLi | CHEMBL203 |
Drug and drug target database More...DrugBanki | DB08916 Afatinib DB03496 Alvocidib DB06021 AV-412 DB12267 Brigatinib DB05424 Canertinib DB00002 Cetuximab DB11963 Dacomitinib DB11731 Depatuxizumab mafodotin DB00530 Erlotinib DB10772 Foreskin keratinocyte (neonatal) DB12010 Fostamatinib DB00317 Gefitinib DB11737 Icotinib DB04988 IGN311 DB01259 Lapatinib DB00281 Lidocaine DB05101 Matuzumab DB07662 N-[4-(3-BROMO-PHENYLAMINO)-QUINAZOLIN-6-YL]-ACRYLAMIDE DB09559 Necitumumab DB11828 Neratinib DB13164 Olmutinib DB09330 Osimertinib DB01269 Panitumumab DB05524 Pelitinib DB05374 Rindopepimut DB07602 S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE DB00072 Trastuzumab DB05294 Vandetanib DB05944 Varlitinib DB12202 Zalutumumab |
DrugCentral More...DrugCentrali | P00533 |
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYi | 1797 |
Polymorphism and mutation databases
BioMuta curated single-nucleotide variation and disease association database More...BioMutai | EGFR |
Domain mapping of disease mutations (DMDM) More...DMDMi | 2811086 |
<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei | 1 – 24 | 3 Publications Manual assertion based on experiment ini
| 24 | |
| <p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000016665 | 25 – 1210 | Epidermal growth factor receptorAdd BLAST | 1186 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi | 31 ↔ 58 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 3 PublicationsManual assertion based on experiment ini
| ||
| <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>GlycosylationiCAR_000227 | 56 | N-linked (GlcNAc...) (complex) asparagine; atypical; partialCombined sources Manual assertion inferred from combination of experimental and computational evidencei 6 PublicationsManual assertion based on experiment ini
| 1 | |
| Glycosylationi | 73 | N-linked (GlcNAc...) asparagine; atypicalCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Glycosylationi | 128 | N-linked (GlcNAc...) asparagine3 Publications Manual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 157 ↔ 187 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 175 | N-linked (GlcNAc...) asparagineCombined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 190 ↔ 199 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 194 ↔ 207 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 196 | N-linked (GlcNAc...) asparagineCombined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 215 ↔ 223 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 219 ↔ 231 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| <p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei | 229 | Phosphoserine1 Publication Manual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 232 ↔ 240 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 236 ↔ 248 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 251 ↔ 260 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 264 ↔ 291 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 295 ↔ 307 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | ||
| Disulfide bondi | 311 ↔ 326 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 329 ↔ 333 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | ||
| Disulfide bondi | 337 ↔ 362 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 352 | N-linked (GlcNAc...) asparagineCombined sources Manual assertion inferred from combination of experimental and computational evidencei 8 PublicationsManual assertion based on experiment ini
| 1 | |
| Glycosylationi | 361 | N-linked (GlcNAc...) asparagineCombined sources Manual assertion inferred from combination of experimental and computational evidencei 6 PublicationsManual assertion based on experiment ini
| 1 | |
| Glycosylationi | 413 | N-linked (GlcNAc...) asparagineCombined sources Manual assertion inferred from combination of experimental and computational evidencei 4 PublicationsManual assertion based on experiment ini
| 1 | |
| Glycosylationi | 444 | N-linked (GlcNAc...) asparagineCombined sources Manual assertion inferred from combination of experimental and computational evidencei 6 PublicationsManual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 470 ↔ 499 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | ||
| Disulfide bondi | 506 ↔ 515 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 510 ↔ 523 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 526 ↔ 535 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 4 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 528 | N-linked (GlcNAc...) asparagineCombined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 539 ↔ 555 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 3 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 558 ↔ 571 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 3 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 562 ↔ 579 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 3 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 568 | N-linked (GlcNAc...) asparagine; partialCombined sources Manual assertion inferred from combination of experimental and computational evidencei 5 PublicationsManual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 582 ↔ 591 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 3 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 595 ↔ 617 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 3 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 603 | N-linked (GlcNAc...) asparagine; partialCombined sources Manual assertion inferred from combination of experimental and computational evidencei 4 PublicationsManual assertion based on experiment ini
| 1 | |
| Disulfide bondi | 620 ↔ 628 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 3 PublicationsManual assertion based on experiment ini
| ||
| Glycosylationi | 623 | N-linked (GlcNAc...) (high mannose) asparagine1 Publication <p>Manually curated information which has been inferred by a curator based on his/her scientific knowledge or on the scientific content of an article.</p> <p><a href="/manual/evidences#ECO:0000305">More...</a></p> Manual assertion inferred by curator fromi
| 1 | |
| Disulfide bondi | 624 ↔ 636 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei 3 PublicationsManual assertion based on experiment ini
| ||
| Modified residuei | 678 | Phosphothreonine; by PKC and PKD/PRKD11 Publication Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 693 | Phosphothreonine; by PKD/PRKD1Combined sources Manual assertion inferred from combination of experimental and computational evidencei
Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 695 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
Manual assertion based on experiment ini
| 1 | |
| <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki | 716 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication Manual assertion based on experiment ini
| ||
| Cross-linki | 737 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication Manual assertion based on experiment ini
| ||
| Cross-linki | 754 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication Manual assertion based on experiment ini
| ||
| Cross-linki | 867 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication Manual assertion based on experiment ini
| ||
| Cross-linki | 929 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication Manual assertion based on experiment ini
| ||
| Cross-linki | 970 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication Manual assertion based on experiment ini
| ||
| Modified residuei | 991 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 995 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | |
| Modified residuei | 998 | Phosphotyrosine; by autocatalysisCombined sources Manual assertion inferred from combination of experimental and computational evidencei
Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 1016 | Phosphotyrosine; by autocatalysis1 Publication Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 1026 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 1039 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | |
| Modified residuei | 1041 | PhosphothreonineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | |
| Modified residuei | 1042 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | |
| <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position(s) and the type of covalently attached lipid group(s).<p><a href='/help/lipid' target='_top'>More...</a></p>Lipidationi | 1049 | S-palmitoyl cysteine1 Publication Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 1064 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | |
| Modified residuei | 1069 | Phosphotyrosine1 Publication Manual assertion inferred by curator fromi
| 1 | |
| Modified residuei | 1070 | Phosphoserine1 Publication Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 1071 | Phosphoserine1 Publication Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 1081 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
|