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Protein Page:
EGFR (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
EGFR a receptor tyrosine kinase. This is a receptor for epidermal growth factor (EGF) and related growth factors including TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30, and vaccinia virus growth factor. EGFR is involved in the control of cell growth and differentiation. It is a single-pass transmembrane tyrosine kinase. Ligand binding to this receptor results in receptor dimerization, autophosphorylation (in trans), activation of various downstream signaling molecules and lysosomal degradation. It can be phosphorylated and activated by Src. Activated EGFR binds the SH2 domain of phospholipase C-gamma (PLC-gamma), activating PLC-gamma-mediated downstream signaling. Phosphorylated EGFR binds Cbl, leading to its ubiquitination and degradation. Grb2 and SHC bind to phospho-EGFR and are involved in the activation of MAP kinase signaling pathways. Phosphorylation on Ser and Thr residues is thought to represent a mechanism for attenuation of EGFR kinase activity. EGFR is overexpressed in breast, head and neck cancers, correlating with poor survival. Activating somatic mutations are seen in lung cancer, corresponding to the minority of patients with strong responses to the EGFR inhibitor Iressa (gefitinib). Mutations and amplifications are also seen in glioblastoma, and upregulation is seen in colon cancer and neoplasms. In xenografts, inhibitors synergize with cytotoxic drugs in the inhibition of many tumor types. Inhibitors include: Iressa/ZD1839, Erbitux, Tarceva, and lapatinib. Four alternatively spliced isoforms have been described. Note: This description may include information from UniProtKB.
Protein type: Protein kinase, TK; Kinase, protein; Membrane protein, integral; Tumor suppressor; EC 2.7.10.1; Protein kinase, tyrosine (receptor); TK group; EGFR family
Chromosomal Location of Human Ortholog: 7p12
Cellular Component: AP-2 adaptor complex; basolateral plasma membrane; cell surface; cytoplasm; early endosome membrane; endosome; endosome membrane; focal adhesion; lipid raft; membrane; nucleus; plasma membrane; receptor complex
Molecular Function: actin filament binding; chromatin binding; enzyme binding; epidermal growth factor receptor activity; identical protein binding; nitric-oxide synthase regulator activity; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; protein binding; protein heterodimerization activity; protein phosphatase binding; protein-tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity; transmembrane receptor activity; transmembrane receptor protein tyrosine kinase activity; ubiquitin protein ligase binding
Biological Process: calcium-dependent phospholipase A2 activation; cell proliferation; cell surface receptor linked signal transduction; cell-cell adhesion; epidermal growth factor receptor signaling pathway; G1/S-specific positive regulation of cyclin-dependent protein kinase activity; learning and/or memory; MAPKKK cascade; negative regulation of apoptosis; negative regulation of epidermal growth factor receptor signaling pathway; negative regulation of protein catabolic process; phosphoinositide-mediated signaling; phospholipase C activation; positive regulation of cell growth; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of DNA repair; positive regulation of DNA replication; positive regulation of epithelial cell proliferation; positive regulation of MAP kinase activity; positive regulation of nitric oxide biosynthetic process; positive regulation of phosphorylation; positive regulation of protein amino acid phosphorylation; positive regulation of protein kinase B signaling cascade; positive regulation of transcription from RNA polymerase II promoter; protein amino acid autophosphorylation; protein insertion into membrane; regulation of nitric-oxide synthase activity; regulation of peptidyl-tyrosine phosphorylation; regulation of phosphoinositide 3-kinase cascade; signal transduction
Disease: Lung Cancer
Reference #:  P00533 (UniProtKB)
Alt. Names/Synonyms: avian erythroblastic leukemia viral (v-erb-b) oncogene homolog; cell growth inhibiting protein 40; cell proliferation-inducing protein 61; EGFR; Epidermal growth factor receptor; epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian); ERBB; ERBB1; HER1; mENA; PIG61; Proto-oncogene c-ErbB-1; Receptor tyrosine-protein kinase erbB-1
Gene Symbols: EGFR
Molecular weight: 134,277 Da
Basal Isoelectric point: 6.26  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  ErbB/HER Signaling  |  IL6 Signaling  |  Phospholipase Signaling  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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EGFR

Protein Structure Not Found.
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Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
apoptosis, inhibited: Y869‑p, Y1092‑p
cell adhesion, altered: Y869‑p, Y1016‑p, Y1092‑p
cell cycle regulation: Y869‑p
cell growth, altered: Y869‑p, Y1092‑p, Y1172‑p, Y1197‑p
cell growth, induced: R222‑m2, R224‑m2, Y1197‑p
cell motility, altered: Y869‑p, Y1016‑p
cell motility, induced: Y1110‑p, Y1197‑p
cytoskeletal reorganization: T678‑p
endocytosis, altered: Y1016‑p
signaling pathway regulation: Y1016‑p
transcription, altered: Y1092‑p, Y1110‑p
activity, induced: Y869‑p, Y1016‑p, Y1092‑p, Y1197‑p
activity, inhibited: S1026‑p
enzymatic activity, induced: R222‑m2, R224‑m2, Y869‑p, Y1016‑p, Y1092‑p, Y1110‑p, Y1172‑p, Y1197‑p
enzymatic activity, inhibited: T678‑p
intracellular localization: R222‑m2, R224‑m2, T678‑p, Y1016‑p, Y1092‑p, Y1110‑p, Y1197‑p
molecular association, regulation: T678‑p, T693‑p, Y727‑p, Y869‑p, Y891‑p, Y978‑p, S991‑p, Y998‑p, Y1016‑p, Y1069‑p, Y1092‑p, Y1110‑p, Y1125‑p, Y1138‑p, Y1172‑p, Y1197‑p
phosphorylation: S991‑p, Y998‑p, Y1016‑p, Y1092‑p, Y1172‑p, Y1197‑p
protein conformation: R222‑m2, R224‑m2, Y1016‑p, Y1092‑p, Y1110‑p
protein degradation: T678‑p, Y1069‑p, Y1092‑p, Y1172‑p, Y1197‑p
receptor desensitization, altered: T678‑p, S1070‑p, S1071‑p
receptor internalization, altered: T678‑p, T693‑p, S695‑p, S991‑p, Y998‑p, Y1016‑p, S1070‑p, S1071‑p, Y1092‑p, Y1110‑p, Y1172‑p, S1190‑p, Y1197‑p
receptor recycling, altered: T678‑p
ubiquitination: Y1069‑p, Y1092‑p, Y1110‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment



 LTP 

LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
41 456 Y1110‑p GsVQNPVyHNQPLNP
0 3 T1145‑p yLNtVQPtCVNStFD
1 10 S1162‑p AHWAQKGsHQIsLDN
0 1 K1188 AkPNGIFKGstAENA
2 0 K713‑ub ILkETEFkkIkVLGs
1 0 K37‑sm VCQGTSNkLTQLGTF
0 1 S77‑p VQRNYDLsFLKTIQE
0 1 Y112‑p QIIRGNMyyENSyAL
0 1 Y113‑p IIRGNMyyENSyALA
0 1 Y117‑p NMyyENSyALAVLSN
0 1 K133‑ac DANKTGLkELPMRNL
0 1 S151‑p LHGAVRFsNNPALCN
1 1 R222‑m2 CAQQCSGrCrGKSPs
1 1 R224‑m2 QQCSGrCrGKSPsDC
1 0 S229‑p rCrGKSPsDCCHNQC
1 0 Y270 TCPPLMLYNPTTYQM
0 1 K284‑ac MDVNPEGkYSFGAtC
0 1 T290‑p GkYSFGAtCVKKCPR
0 1 Y316 RACGADSYEMEEDGV
0 1 K346‑ac GIGIGEFkDSLSINA
0 1 K454 SLGLRSLKEIsDGDV
0 1 S457‑p LRSLKEIsDGDVIIS
0 1 K487 LFGTSGQKTKIISNR
0 1 S511‑p QVCHALCsPEGCWGP
0 1 Y585‑p NCIQCAHyIDGPHCV
0 2 S645‑p TNGPKIPsIAtGMVG
0 2 T648‑p PKIPsIAtGMVGALL
19 0 T678‑p RHIVRKRtLRRLLQE
14 68 T693‑p RELVEPLtPsGEAPN
5 8 S695‑p LVEPLtPsGEAPNQA
1 2 K708‑ub QALLRILkETEFkkI
2 0 K714‑ub LkETEFkkIkVLGsG
3 0 K716‑ub ETEFkkIkVLGsGAF
0 1 S720‑p kkIkVLGsGAFGtVy
1 6 T725‑p LGsGAFGtVykGLWI
3 147 Y727‑p sGAFGtVykGLWIPE
1 1 K728‑ub GAFGtVykGLWIPEG
3 2 K737‑ub LWIPEGEkVkIPVAI
1 1 K739‑ub IPEGEkVkIPVAIKE
0 1 K745 VkIPVAIKELREATs
0 1 S752‑p KELREATsPkANkEI
2 0 K754‑ub LREATsPkANkEILD
3 1 K757‑ub ATsPkANkEILDEAy
2 7 Y764‑p kEILDEAyVMAsVDN
3 0 S768‑p DEAyVMAsVDNPHVC
0 2 Y801‑p PFGCLLDyVREHKDN
1 0 K823‑ub NWCVQIAkGMNyLED
0 1 Y827‑p QIAkGMNyLEDRRLV
1 1 K846‑ub AARNVLVkTPQHVKI
0 1 K852 VkTPQHVKITDFGLA
1 4 K860‑ub ITDFGLAkLLGAEEk
3 1 K867‑ub kLLGAEEkEyHAEGG
75 163 Y869‑p LGAEEkEyHAEGGkV
1 2 K875‑ub EyHAEGGkVPIKWMA
1 0 Y891‑p ESILHRIytHQSDVW
1 0 T892‑p SILHRIytHQSDVWS
1 0 K913‑ub ELMTFGSkPYDGIPA
2 1 K929‑ub EISSILEkGERLPQP
0 1 Y944‑p PICTIDVyMIMVKCW
1 0 K960‑ub IDADSRPkFRELIIE
3 1 K970‑ub ELIIEFSkMARDPQR
1 5 Y978‑p MARDPQRyLVIQGDE
3 31 S991‑p DERMHLPsPtDsNFy
0 11 T993‑p RMHLPsPtDsNFyRA
1 14 S995‑p HLPsPtDsNFyRALM
4 145 Y998‑p sPtDsNFyRALMDEE
43 9 Y1016‑p DVVDADEyLIPQQGF
1 2 S1025‑p IPQQGFFssPSTsRt
2 5 S1026‑p PQQGFFssPSTsRtP
0 1 S1030‑p FFssPSTsRtPLLSs
0 3 T1032‑p ssPSTsRtPLLSsLs
2 4 S1037‑p sRtPLLSsLsAtsNN
2 9 S1039‑p tPLLSsLsAtsNNst
2 3 T1041‑p LLSsLsAtsNNstVA
2 10 S1042‑p LSsLsAtsNNstVAC
1 5 S1045‑p LsAtsNNstVACIDR
0 3 T1046‑p sAtsNNstVACIDRN
1 4 S1057‑p IDRNGLQsCPIkEDs
1 0 K1061‑ac GLQsCPIkEDsFLQR
1 1 K1061‑ub GLQsCPIkEDsFLQR
2 13 S1064‑p sCPIkEDsFLQRyss
37 130 Y1069‑p EDsFLQRyssDPtGA
13 10 S1070‑p DsFLQRyssDPtGAL
12 8 S1071‑p sFLQRyssDPtGALt
0 3 T1074‑p QRyssDPtGALtEDs
0 1 T1078‑p sDPtGALtEDsIDDt
4 7 S1081‑p tGALtEDsIDDtFLP
0 3 T1085‑p tEDsIDDtFLPVPEy
112 357 Y1092‑p tFLPVPEyINQsVPK
1 4 S1096‑p VPEyINQsVPKRPAG
1 10 S1104‑p VPKRPAGsVQNPVyH
0 9 S1120‑p QPLNPAPsRDPHyQD
4 37 Y1125‑p APsRDPHyQDPHstA
0 6 S1130‑p PHyQDPHstAVGNPE
0 4 T1131‑p HyQDPHstAVGNPEy
3 66 Y1138‑p tAVGNPEyLNtVQPt
0 2 T1141‑p GNPEyLNtVQPtCVN
0 1 T1150‑p QPtCVNStFDsPAHW
0 5 S1153‑p CVNStFDsPAHWAQK
3 96 S1166‑p QKGsHQIsLDNPDyQ
42 989 Y1172‑p IsLDNPDyQQDFFPk
1 0 K1179‑ac yQQDFFPkEAkPNGI
0 1 K1179 yQQDFFPKEAkPNGI
1 0 K1182‑ac DFFPkEAkPNGIFkG
0 1 K1182 DFFPkEAKPNGIFkG
1 0 K1188‑ac AkPNGIFkGstAENA
2 3 S1190‑p PNGIFkGstAENAEy
1 4 T1191‑p NGIFkGstAENAEyL
84 1037 Y1197‑p stAENAEyLRVAPQS
2220 : Phospho-EGF Receptor (Tyr1086) Antibody
14343 : Phospho-EGF Receptor (Thr678) Antibody
3056 : Phospho-EGF Receptor (Thr669) Antibody
8808 : Phospho-EGF Receptor (Thr669) (D2F1) Rabbit mAb
2231 : Phospho-EGF Receptor (Tyr845) Antibody
6963 : Phospho-EGF Receptor (Tyr845) (D63B4) Rabbit mAb
2641 : Phospho-EGF Receptor (Tyr998) (C24A5) Rabbit mAb
2235 : Phospho-EGF Receptor (Tyr992) Antibody
2237 : Phospho-EGF Receptor (Tyr1045) Antibody
2238 : Phospho-EGF Receptor (Ser1046/1047) Antibody
2238 : Phospho-EGF Receptor (Ser1046/1047) Antibody
2234 : Phospho-EGF Receptor (Tyr1068) Antibody
2236 : Phospho-EGF Receptor (Tyr1068) (1H12) Mouse mAb
3777 : Phospho-EGF Receptor (Tyr1068) (D7A5) XP(R) Rabbit mAb
4031 : Phospho-EGF Receptor (Tyr1068) (1H12) Mouse mAb (Biotinylated)
8543 : Phospho-EGF Receptor (Tyr1068) (D7A5) XP(R) Rabbit mAb (Biotinylated)
14565 : Phospho-EGF Receptor (Tyr1068) (D7A5) XP(R) Rabbit mAb (PE Conjugate)
4404 : Phospho-EGF Receptor (Tyr1148) Antibody
2244 : Phospho-HER2/ErbB2 (Tyr1248)/EGFR (Tyr1173) Antibody
4407 : Phospho-EGF Receptor (Tyr1173) (53A5) Rabbit mAb
  EGFR iso2  
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K37 VCQGTSNKLTQLGTF
S77 VQRNYDLSFLKTIQE
Y112 QIIRGNMYYENSYAL
Y113 IIRGNMYYENSYALA
Y117 NMYYENSYALAVLSN
K133 DANKTGLKELPMRNL
S151 LHGAVRFSNNPALCN
R222 CAQQCSGRCRGKSPS
R224 QQCSGRCRGKSPSDC
S229 RCRGKSPSDCCHNQC
Y270 TCPPLMLYNPTTYQM
K284 MDVNPEGKYSFGATC
T290 GKYSFGATCVKKCPR
Y316 RACGADSYEMEEDGV
K346 GIGIGEFKDSLSINA
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  EGFR iso5  
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K713 ILKETEFKKIKVLGS
K37 VCQGTSNKLTQLGTF
S77 VQRNYDLSFLKTIQE
Y112 QIIRGNMYYENSYAL
Y113 IIRGNMYYENSYALA
Y117 NMYYENSYALAVLSN
K133 DANKTGLKELPMRNL
S151 LHGAVRFSNNPALCN
R222 CAQQCSGRCRGKSPS
R224 QQCSGRCRGKSPSDC
S229 RCRGKSPSDCCHNQC
Y270 TCPPLMLYNPTTYQM
K284 MDVNPEGKYSFGATC
T290 GKYSFGATCVKKCPR
Y316 RACGADSYEMEEDGV
K346 GIGIGEFKDSLSINA
K454 SLGLRSLKEISDGDV
S457 LRSLKEISDGDVIIS
K487 LFGTSGQKTKIISNR
S511 QVCHALCSPEGCWGP
Y585 NCIQCAHYIDGPHCV
S645 TNGPKIPSIATGMVG
T648 PKIPSIATGMVGALL
T678 RHIVRKRTLRRLLQE
T693 RELVEPLTPSGEAPN
S695 LVEPLTPSGEAPNQA
K708 QALLRILKETEFKKI
K714 LKETEFKKIKVLGSG
K716 ETEFKKIKVLGSGAF
S720 KKIKVLGSGAFGTVY
T725 LGSGAFGTVYKGLWI
Y727 SGAFGTVYKGLWIPE
K728 GAFGTVYKGLWIPEG
K737 LWIPEGEKVKIPVAI
K739 IPEGEKVKIPVAIKE
K745 VKIPVAIKELREATS
S752 KELREATSPKANKEI
K754 LREATSPKANKEILD
K757 ATSPKANKEILDEAY
Y764 KEILDEAYVMASVDN
S768 DEAYVMASVDNPHVC
Y801 PFGCLLDYVREHKDN
K823 NWCVQIAKGMNYLED
Y827 QIAKGMNYLEDRRLV
K846 AARNVLVKTPQHVKI
K852 VKTPQHVKITDFGLA
K860 ITDFGLAKLLGAEEK
K867 KLLGAEEKEYHAEGG
Y869 LGAEEKEYHAEGGKV
K875 EYHAEGGKVPIKWMA
Y891 ESILHRIYTHQSDVW
T892 SILHRIYTHQSDVWS
K913 ELMTFGSKPYDGIPA
K929 EISSILEKGERLPQP
Y944 PICTIDVYMIMVKCW
K960 IDADSRPKFRELIIE
K970 ELIIEFSKMARDPQR
Y978 MARDPQRYLVIQGDE
S991 DERMHLPSPTDSNFY
T993 RMHLPSPTDSNFYRA
S995 HLPSPTDSNFYRALM
Y998 SPTDSNFYRALMDEE
Y1016 DVVDADEYLIPQQGF
S1025 IPQQGFFSSPSTSRT
S1026 PQQGFFSSPSTSRTP
S1030 FFSSPSTSRTPLLSS
T1032 SSPSTSRTPLLSSLS
S1037 SRTPLLSSLSATSNN
S1039 TPLLSSLSATSNNST
T1041 LLSSLSATSNNSTVA
S1042 LSSLSATSNNSTVAC
S1045 LSATSNNSTVACIDR
T1046 SATSNNSTVACIDRN
S1057 IDRNGLQSCPIKEDS
K1061 GLQSCPIKEDSFLQR
K1061 GLQSCPIKEDSFLQR
S1064 SCPIKEDSFLQRYSS
Y1069 EDSFLQRYSSDPTGA
S1070 DSFLQRYSSDPTGAL
S1071 SFLQRYSSDPTGALT
T1074 QRYSSDPTGALTEDS
T1078 SDPTGALTEDSIDDT
S1081 TGALTEDSIDDTFLP
T1085 TEDSIDDTFLPVPGE
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2238 : Phospho-EGF Receptor (Ser1046/1047) Antibody
2238 : Phospho-EGF Receptor (Ser1046/1047) Antibody
  mouse