P00533

※ Protein Information

Tag	Content
UniProt Accession	EGFR_HUMAN; P00533;
Entrez ID	1956
GenBank Protein ID	NM_005228.4; NM_201282.1; NM_201283.1; NM_201284.1;
GenBank Nucleotide ID	NP_005219.2; NP_958439.1; NP_958440.1; NP_958441.1;
Protein Name	Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1)
Gene Name	EGFR; ERBB; ERBB1; HER1
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Ac(view all) Functional Description Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Plays a role in enhancing learning and memory performance (By similarity).;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.
Sequence (Fasta)	MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV 60 VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA 120 VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF 180 QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC 240 TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV 300 VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK 360 NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF 420 ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL 480 FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN 540 LLEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM 600 GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCPTNG PKIPSIATGM VGALLLLLVV 660 ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEAPN QALLRILKET EFKKIKVLGS 720 GAFGTVYKGL WIPEGEKVKI PVAIKELREA TSPKANKEIL DEAYVMASVD NPHVCRLLGI 780 CLTSTVQLIT QLMPFGCLLD YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA 840 RNVLVKTPQH VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY 900 GVTVWELMTF GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC WMIDADSRPK 960 FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA LMDEEDMDDV VDADEYLIPQ 1020 QGFFSSPSTS RTPLLSSLSA TSNNSTVACI DRNGLQSCPI KEDSFLQRYS SDPTGALTED 1080 SIDDTFLPVP EYINQSVPKR PAGSVQNPVY HNQPLNPAPS RDPHYQDPHS TAVGNPEYLN 1140 TVQPTCVNST FDSPAHWAQK GSHQISLDNP DYQQDFFPKE AKPNGIFKGS TAENAEYLRV 1200 APQSSEFIGA 1211 Fasta Sequence >P00533\|EGFR; ERBB; ERBB1; HER1\|Homo sapiens (Human) MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLNTVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRVAPQSSEFIGA

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Phosphorylation	B-chronic lymphocytic leukemia		A		23866081
1	[Reference]: CLL cells did not express EGFR and nonspecific staining with anti-phospho-EGFR antibodies was not observed
2	Phosphorylation	Thyroid cancer/carcinoma		D		16822827
2	[Reference]: EGFR expression and phosphorylation in the thyroid carcinoma cell lines and tissue specimens were present but not stronger than in noncancerous thyroid tissue.
3	Phosphorylation	Lung adenocarcinoma		P		23866081
3	[Reference]: Constitutive phosphorylation of EGFR at Y-845 in Calu3 and H1975 cell lines, and at Y-992 was seen in Calu3, H1975, and A549 cell lines
4	Phosphorylation	Epidermoid carcinoma	cell line	P		23499740
4	[Reference]: he results indicated that hIgG38 binding to L1 and hIgG45 binding to C2 substantially suppressed the EGF-induced phosphorylation of EGFR, resulting in the growth inhibition of A431 cancer cells
5	Phosphorylation	Thyroid cancer/carcinoma		P		11299771
5	[Reference]: We have previously reported that apigenin inhibits the growth of thyroid cancer cells by attenuating epidermal growth factor receptor (EGF-R) tyrosine phosphorylation and phosphorylation of ERK mitogen-activated protein (MAP) kinase.
6	Phosphorylation	Ovarian cancer/carcinoma		U		22952709
6	[Reference]: PEITC treatment caused significant down regulation of constitutive protein levels as well as phosphorylation of EGFR at Tyr1068 in various ovarian cancer cells
7	Phosphorylation	Colon cancer/carcinoma		U		24665413
7	[Reference]: phosphorylation of Threonine 192 in Claudin-3 leads to disruption of TJs in an ovarian cancer cell line24 and increased phosphorylation of its C-terminal tyrosines was found in EGFR and c-MET positive colon cancer cells
8	Phosphorylation	Head and neck squamous cell carcinoma		U		23799848
8	[Reference]: Ron+HNSCC also had significantly higher EGFR expression and correlated strongly with phosphorylated EGFR (pEGFR)
9	Phosphorylation	Glioma/Adult gliomas		U		24403856
9	[Reference]: The deltaEGFR-expressing U87 xenografts showed a high level of EGFR Y1173 phosphorylation compared to the low level seen in control U87 tumors. These results are consistent with in vitro experiments using these cell lines, which demonstrate high levels of constitutive EGFR Y1173 phosphorylation and low but EGF-inducible Y1173 phosphorylation of the endogenous, wild-type receptor
10	Phosphorylation	Glioblastoma		C		24346432
10	[Reference]: EGFR phosphorylation was increased only in LCM-enriched tumor specimens carrying EGFR mutations. Phosphorylated and total PTEN, which is highly expressed in normal brain, was reduced only in LCM-enriched tumor specimens with either PTEN mutation or loss in PTEN copy number, with no differences observed in non-microdissected samples.
11	Serine Phosphorylation	Esophageal squamous cell carcinoma		N	S768	16357520
11	[Reference]: As demonstrated by in vitro proliferation assay, this mutation sensitized Kyse450 cells to gefitinib. The observation of down regulation of the phosphorylated pAKT indicated gefitinib induced Kyse450 cells apoptosis via inhibition of EGFR activity
12	Serine Phosphorylation	Non-small cell lung cancer/carcinoma	cell line	N	S768	17653080
12	[Reference]: S768I and L861Q mutants were less sensitive to Src suppression than others. Mutation at tyrosine 869 (845) residue, an Src phosphorylation site, decreased the phosphorylation levels of wild-type EGFR and other mutants, but not that of S768I and L861Q mutants, suggesting that S768I and L861Q mutants became Src independent for their activation and biological functions.
13	Threonine Phosphorylation	Non-small cell lung cancer/carcinoma		N	T790	18199554
13	[Reference]: Of note, EGFR T790M, a receptor variant found in patients with gefitinib-resistant NSCLC, was also resistant to lapatinib-mediated inhibition of receptor autophosphorylation.
14	Tyrosine Phosphorylation	Lung adenocarcinoma		P	Y845	23866081
14	[Reference]: Constitutive phosphorylation of EGFR at Y-845 in Calu3 and H1975 cell lines, and at Y-992 was seen in Calu3, H1975, and A549 cell lines
15	Tyrosine Phosphorylation	Breast cancer/tumor/carcinoma		P	Y845	22179831; 23066441
15	[Reference]: EGFR Tyrosine 845 Phosphorylation-Dependent Proliferation and Transformation of Breast Cancer Cells Require Activation of p38 MAPK
16	Tyrosine Phosphorylation	Liver cancer	cell line	P	Y845	23220047
16	[Reference]: The COOH-terminus of TM4SF5 in hepatoma cell lines regulates c-Src to form invasive protrusions via EGFR Tyr845 phosphorylation
17	Tyrosine Phosphorylation	Non-small cell lung cancer/carcinoma		U	Y869	17653080; 16505275
17	[Reference]: Mutation at tyrosine 869 (845) residue, an Src phosphorylation site, decreased the phosphorylation levels of wild-type EGFR and other mutants, but not that of S768I and L861Q mutants, suggesting that S768I and L861Q mutants became Src independent for their activation and biological functions.
18	Tyrosine Phosphorylation	Gastric cancer	AGS cell line	P	Y992	23613900
18	[Reference]: PKG II inhibited EGF-induced migration activity and blocked EGF-initiated signal transduction of PLC1 and MAPK/ERK-mediated pathways through preventing EGF-induced Tyr 992 and Tyr 1068 phosphorylation of EGFR. PKG II bound with EGFR and caused threonine phosphorylation of it
19	Tyrosine Phosphorylation	Non-small cell lung cancer/carcinoma		U	Y1016	19002495
19	[Reference]: Epidermal growth factor receptor mutations in non-small cell lung cancer influence downstream Akt, MAPK and Stat3 signaling.
20	Tyrosine Phosphorylation	Breast cancer/tumor/carcinoma	cell line	C	Y1045	16969069
20	[Reference]: These results suggest that hypophosphorylation of tyrosine residue 1045 is likely to be the cause for EGFRvIII escape from c-Cbl-induced ubiquitination and degradation, enhancing EGFRvIII?? ability to increase proliferation in breast cancer cells
21	Serine Phosphorylation	Non-small cell lung cancer/carcinoma	tumor tissue	U	S1046	23520446
21	[Reference]: The expression of pEGFR-Ser1046 and AURKA was significantly higher in tumors than in the adjacent normal tissue (p = 0.001) of 25 NSCLC patients
22	Tyrosine Phosphorylation	Non-small cell lung cancer/carcinoma	cell line	P	Y1068	22901364
22	[Reference]: Phosphorylated EGFR expression may predict outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild-type EGFR
23	Tyrosine Phosphorylation	Gastric cancer	AGS cell line	P	Y1068	23613900
23	[Reference]: PKG II inhibited EGF-induced migration activity and blocked EGF-initiated signal transduction of PLC1 and MAPK/ERK-mediated pathways through preventing EGF-induced Tyr 992 and Tyr 1068 phosphorylation of EGFR. PKG II bound with EGFR and caused threonine phosphorylation of it
24	Tyrosine Phosphorylation	Tonsillar cancer	tumor tissue	P	Y1068	23564800
24	[Reference]: Since pEGFR Tyr1068 and 1148 are correlated to absence of HPV but not to clinical outcome, these may not be optimal prognostic markers for clinical outcome in patients with TSCC
25	Tyrosine Phosphorylation	Prostate cancer/carcinoma/adenocarcinoma	tumor tissue	U	Y1068	22307624
25	[Reference]: Tyrosine Phosphorylation Is Increased in Clinical Castration-Resistant Prostate Cancer Samples
26	Tyrosine Phosphorylation	Non-small cell lung cancer/carcinoma		D	Y1069	18687633
26	[Reference]: Laser capture microdissection and protein microarray analysis of human non-small cell lung cancer: differential epidermal growth factor receptor (EGPR) phosphorylation events associated with mutated EGFR compared with wild type.
27	Tyrosine Phosphorylation	Breast cancer/tumor/carcinoma		U	Y1086	22222162
27	[Reference]: We found that there was an increase in phosphorylation of pY1086 EGFR after 18 h EtOH treatment in CYP2E1 overexpressing cells. These studies support a hypothesis that EtOH might increase human mammary cell activation, via an EGFR-dependent signaling mechanism associated with oxidative stress
28	Tyrosine Phosphorylation	Non-small cell lung cancer/carcinoma		U	Y1092	17653080; 18687633; 28724430
28	[Reference]: EGFR modulates monounsaturated fatty acid synthesis through phosphorylation of SCD1 in lung cancer.
29	Tyrosine Phosphorylation	Tonsillar cancer	tumor tissue	P	Y1148	23564800
29	[Reference]: Since pEGFR Tyr1068 and 1148 are correlated to absence of HPV but not to clinical outcome, these may not be optimal prognostic markers for clinical outcome in patients with TSCC
30	Serine Phosphorylation	Lung cancer/carcinoma		P	S1166	22703031
30	[Reference]: EGFR S1166 phosphorylation induced by a combination of EGF and gefitinib has a potentially negative impact on lung cancer cell growth
31	Tyrosine Phosphorylation	Non-small cell lung cancer/carcinoma		U	Y1172	18687633
31	[Reference]: Laser capture microdissection and protein microarray analysis of human non-small cell lung cancer: differential epidermal growth factor receptor (EGPR) phosphorylation events associated with mutated EGFR compared with wild type.
32	Arginine Methylation	Breast cancer/tumor/carcinoma	MCF7 cell line	A	R1175	21258366
32	[Reference]: Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays, we observed that MCF7-EGFR (R1175K) cells grew more quickly than MCF7-EGFR (WT) cell
33	Tyrosine Phosphorylation	Non-small cell lung cancer/carcinoma		U	Y1197	19002495
33	[Reference]: Epidermal growth factor receptor mutations in non-small cell lung cancer influence downstream Akt, MAPK and Stat3 signaling.

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association