P00533 (EGFR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	EGFR
Synonyms:	ERBB, ERBB1, HER1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1210 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Ref.29 Ref.35 Ref.36 Ref.39 Ref.40 Ref.41 Ref.49 Ref.66 Ref.68 Ref.69 Ref.70 Ref.77 Ref.79 Isoform 2 may act as an antagonist of EGF action. Ref.29 Ref.35 Ref.36 Ref.39 Ref.40 Ref.41 Ref.49 Ref.66 Ref.68 Ref.69 Ref.70 Ref.77 Ref.79
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.70 Ref.73 Ref.74 Ref.75 Ref.76 Ref.77
Enzyme regulation	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. Ref.37 Ref.42 Ref.60 Ref.74
Subunit structure	Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. Heterodimer with ERBB2. Interacts with ERRFI1; inhibits dimerization of the kinase domain and autophosphorylation. Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B. Interacts with GRB2; an adapter protein coupling the receptor to downstream signaling pathways. Interacts with GAB2; involved in signaling downstream of EGFR. Interacts with STAT3; mediates EGFR downstream signaling in cell proliferation. Interacts with RIPK1; involved in NF-kappa-B activation. Interacts (autophosphorylated) with CBL; involved in EGFR ubiquitination and regulation. Interacts with SOCS5; regulates EGFR degradation through TCEB1- and TCEB2-mediated ubiquitination and proteasomal degradation. Interacts with PRMT5; methylates EGFR and enhances interaction with PTPN6. Interacts (phosphorylated) with PTPN6; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with COPG; essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER. Interacts with TNK2; this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts with PCNA; positively regulates PCNA. Interacts with PELP1. Interacts with MUC1. Interacts with AP2M1. Interacts with FER. May interact with EPS8; mediates EPS8 phosphorylation. Interacts (via SH2 domains) with GRB2, NCK1 and NCK2. Ref.29 Ref.32 Ref.33 Ref.36 Ref.37 Ref.39 Ref.40 Ref.41 Ref.42 Ref.47 Ref.49 Ref.52 Ref.55 Ref.60 Ref.64 Ref.66 Ref.67 Ref.68 Ref.69 Ref.74 Ref.76 Ref.77 Ref.78 Ref.79
Subcellular location	Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Nucleus membrane; Single-pass type I membrane protein. Endosome. Endosome membrane. Note: In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand. Ref.49 Ref.52 Ref.60 Ref.64 Ref.68 Ref.77 Isoform 2: Secreted Ref.49 Ref.52 Ref.60 Ref.64 Ref.68 Ref.77.
Tissue specificity	Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers. Ref.51
Post-translational modification	Phosphorylation at Ser-695 is partial and occurs only if Thr-693 is phosphorylated. Phosphorylation at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis and stabilizes the receptor at the plasma membrane. Autophosphorylation at Tyr-1197 is stimulated by methylation at Arg-1199 and enhances interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 recruits STAT3. Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occur. Methylated. Methylation at Arg-1199 by PRMT5 positively stimulates phosphorylation at Tyr-1197. Ref.66
Involvement in disease	Defects in EGFR are associated with lung cancer (LNCR) [MIM:211980]. LNCR is a 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.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Membrane Nucleus Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Tumor suppressor
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Isopeptide bond Methylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	activation of phospholipase A2 activity by calcium-mediated signaling Traceable author statement. Source: UniProtKB activation of phospholipase C activity Traceable author statement. Source: UniProtKB axon guidance Traceable author statement. Source: Reactome cell proliferation Inferred from direct assay Ref.49. Source: UniProtKB cell-cell adhesion Inferred from mutant phenotype. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype. Source: UniProtKB negative regulation of epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome negative regulation of protein catabolic process Inferred from direct assay Ref.49. Source: UniProtKB ossification Non-traceable author statement. Source: UniProtKB positive regulation of DNA repair Inferred from direct assay Ref.49. Source: UniProtKB positive regulation of DNA replication Inferred from direct assay Ref.49. Source: UniProtKB positive regulation of MAP kinase activity Inferred from direct assay. Source: UniProtKB positive regulation of catenin import into nucleus Inferred from mutant phenotype. Source: BHF-UCL positive regulation of cell migration Inferred from mutant phenotype. Source: UniProtKB positive regulation of cyclin-dependent protein kinase activity involved in G1/S Inferred from direct assay. Source: BHF-UCL positive regulation of epithelial cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of nitric oxide biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of phosphorylation Inferred from direct assay. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from mutant phenotype. Source: BHF-UCL protein autophosphorylation Inferred from mutant phenotype. Source: UniProtKB protein insertion into membrane Traceable author statement. Source: UniProtKB regulation of nitric-oxide synthase activity Inferred from direct assay. Source: UniProtKB regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype. Source: UniProtKB response to UV-A Inferred from direct assay. Source: BHF-UCL response to stress Non-traceable author statement. Source: UniProtKB
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell Shc-EGFR complex Inferred from sequence or structural similarity. Source: BHF-UCL basolateral plasma membrane Inferred from direct assay. Source: BHF-UCL endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endosome Inferred from direct assay Ref.52. Source: UniProtKB extracellular space Non-traceable author statement Ref.4. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane raft Inferred from direct assay. Source: UniProtKB nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP/ERK kinase kinase activity Non-traceable author statement. Source: UniProtKB actin filament binding Inferred from direct assay. Source: UniProtKB double-stranded DNA binding Non-traceable author statement Ref.22. Source: UniProtKB epidermal growth factor-activated receptor activity Inferred from direct assay Ref.49. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct protein heterodimerization activity Inferred from direct assay. Source: UniProtKB protein phosphatase binding Inferred from physical interaction. Source: UniProtKB receptor signaling protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		10	EBI-297353,EBI-297353
AKAP12	Q02952	2	EBI-297353,EBI-2562430
CALM1	P62158	3	EBI-297353,EBI-397435
Calm1	P62161	6	EBI-297353,EBI-397530	From a different organism.
CBL	P22681	4	EBI-297353,EBI-518228
Cbl	P22682	2	EBI-297353,EBI-640919	From a different organism.
CYTH2	Q99418	5	EBI-297353,EBI-448974
EGF	P01133	3	EBI-297353,EBI-640857
ERBB2	P04626	9	EBI-297353,EBI-641062
ERBB3	P21860	3	EBI-297353,EBI-720706
ERBB4	Q15303	2	EBI-297353,EBI-80371
ERRFI1	Q9UJM3	2	EBI-297353,EBI-2941912
ESR1	P03372-4	4	EBI-297353,EBI-4309277
FKBP8	Q14318	3	EBI-297353,EBI-724839
GABARAPL2	P60520	2	EBI-297353,EBI-720116
GAPDH	P04406	4	EBI-297353,EBI-354056
GRB2	P62993	12	EBI-297353,EBI-401755
HDAC6	Q9UBN7	8	EBI-297353,EBI-301697
HSPA1A	P08107	4	EBI-297353,EBI-629985
MAST1	Q9Y2H9	2	EBI-297353,EBI-3385920
MET	P08581	4	EBI-297353,EBI-1039152
PIK3C2B	O00750	7	EBI-297353,EBI-641107
RABGEF1	Q9UJ41	4	EBI-297353,EBI-913954
RIN1	Q13671	3	EBI-297353,EBI-366017
SHC1	P29353	5	EBI-297353,EBI-78835
SLC5A1	P13866	3	EBI-297353,EBI-1772443
SRC	P12931	5	EBI-297353,EBI-621482
STIP1	P31948	2	EBI-297353,EBI-1054052
Trpv3	Q8K424	2	EBI-297353,EBI-2650739	From a different organism.
UCHL1	P09936	2	EBI-297353,EBI-714860
VAPA	Q9P0L0	2	EBI-297353,EBI-1059156
YWHAQ	P27348	4	EBI-297353,EBI-359854
YWHAZ	P63104	4	EBI-297353,EBI-347088

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P00533-1)

Also known as: p170;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P00533-2)

Also known as: p60; Truncated; TEGFR;

The sequence of this isoform differs from the canonical sequence as follows:
     404-405: FL → LS
     406-1210: Missing.

Isoform 3 (identifier: P00533-3)

Also known as: p110;

The sequence of this isoform differs from the canonical sequence as follows:
     628-705: CTGPGLEGCP...GEAPNQALLR → PGNESLKAML...SVIITASSCH
     706-1210: Missing.

Isoform 4 (identifier: P00533-4)

The sequence of this isoform differs from the canonical sequence as follows:
     628-628: C → S
     629-1210: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Ref.18

Chain

25 – 1210

1186

Epidermal growth factor receptor

PRO_0000016665

Regions

Topological domain

25 – 645

621

Extracellular Potential

Transmembrane

646 – 668

23

Helical; Potential

Topological domain

669 – 1210

542

Cytoplasmic Potential

Repeat

75 – 300

226

Approximate

Repeat

390 – 600

211

Approximate

Domain

712 – 979

268

Protein kinase

Nucleotide binding

718 – 726

9

ATP

Nucleotide binding

790 – 791

2

ATP

Region

688 – 704

17

Important for dimerization, phosphorylation and activation

Compositional bias

1025 – 1071

47

Ser-rich

Sites

Active site

837

1

Proton acceptor By similarity

Binding site

745

1

ATP

Binding site

855

1

ATP

Site

1016

1

Important for interaction with PIK3C2B

Amino acid modifications

Modified residue

678

1

Phosphothreonine; by PKC and PKD/PRKD1

Modified residue

693

1

Phosphothreonine; by PKD/PRKD1

Modified residue

695

1

Phosphoserine Ref.17 Ref.57 Ref.58

Modified residue

725

1

Phosphothreonine Ref.57

Modified residue

869

1

Phosphotyrosine Ref.50

Modified residue

978

1

Phosphotyrosine Ref.46

Modified residue

991

1

Phosphoserine Ref.44 Ref.48 Ref.54 Ref.56 Ref.57 Ref.58

Modified residue

993

1

Phosphothreonine Ref.58

Modified residue

995

1

Phosphoserine Ref.48 Ref.58

Modified residue

998

1

Phosphotyrosine; by autocatalysis Ref.45 Ref.48 Ref.54 Ref.58 Ref.62 Ref.76

Modified residue

1016

1

Phosphotyrosine; by autocatalysis Ref.62 Ref.76

Modified residue

1025

1

Phosphoserine Ref.57

Modified residue

1026

1

Phosphoserine Ref.44 Ref.57

Modified residue

1037

1

Phosphoserine Ref.57

Modified residue

1039

1

Phosphoserine Ref.57 Ref.58

Modified residue

1041

1

Phosphothreonine Ref.58

Modified residue

1042

1

Phosphoserine Ref.57 Ref.58

Modified residue

1045

1

Phosphoserine Ref.58

Modified residue

1064

1

Phosphoserine Ref.48 Ref.57 Ref.58

Modified residue

1069

1

Phosphotyrosine Ref.45 Ref.48 Ref.54

Modified residue

1070

1

Phosphoserine Ref.17

Modified residue

1071

1

Phosphoserine Ref.17

Modified residue

1081

1

Phosphoserine Ref.57

Modified residue

1092

1

Phosphotyrosine; by autocatalysis Ref.36 Ref.45 Ref.48 Ref.50 Ref.62

Modified residue

1110

1

Phosphotyrosine; by autocatalysis Ref.25 Ref.36 Ref.48 Ref.62

Modified residue

1138

1

Phosphotyrosine Ref.48 Ref.62

Modified residue

1166

1

Phosphoserine Ref.45 Ref.54 Ref.57 Ref.58

Modified residue

1172

1

Phosphotyrosine; by autocatalysis Ref.45 Ref.48 Ref.50 Ref.54 Ref.62

Modified residue

1197

1

Phosphotyrosine; by autocatalysis Ref.48 Ref.50 Ref.54 Ref.57 Ref.62 Ref.76

Modified residue

1199

1

Omega-N-methylated arginine Ref.66

Glycosylation

56

1

N-linked (GlcNAc...) (complex); atypical; partial Ref.34 Ref.44 Ref.68 Ref.79

CAR_000227

Glycosylation

73

1

N-linked (GlcNAc...) Ref.79

Glycosylation

128

1

N-linked (GlcNAc...) Ref.30 Ref.44

Glycosylation

175

1

N-linked (GlcNAc...) Ref.30 Ref.44 Ref.68 Ref.79

Glycosylation

196

1

N-linked (GlcNAc...) Ref.44 Ref.68 Ref.79

Glycosylation

352

1

N-linked (GlcNAc...) Ref.34 Ref.44 Ref.61 Ref.68 Ref.69 Ref.79

Glycosylation

361

1

N-linked (GlcNAc...) Ref.34 Ref.44 Ref.68 Ref.69 Ref.79

Glycosylation

413

1

N-linked (GlcNAc...) Ref.30 Ref.44 Ref.61

Glycosylation

444

1

N-linked (GlcNAc...) Ref.30 Ref.44 Ref.68 Ref.69 Ref.79

Glycosylation

528

1

N-linked (GlcNAc...) Ref.30 Ref.44 Ref.69 Ref.79

Glycosylation

568

1

N-linked (GlcNAc...); partial Ref.34 Ref.44 Ref.61 Ref.69

Glycosylation

603

1

N-linked (GlcNAc...); partial Ref.34 Ref.44 Ref.69

Disulfide bond

31 ↔ 58

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

157 ↔ 187

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

190 ↔ 199

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

194 ↔ 207

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

215 ↔ 223

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

219 ↔ 231

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

232 ↔ 240

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

236 ↔ 248

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

251 ↔ 260

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

264 ↔ 291

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

295 ↔ 307

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

311 ↔ 326

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

329 ↔ 333

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

337 ↔ 362

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

470 ↔ 499

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

506 ↔ 515

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

510 ↔ 523

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

526 ↔ 535

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

539 ↔ 555

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

558 ↔ 571

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

562 ↔ 579

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

582 ↔ 591

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

595 ↔ 617

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

620 ↔ 628

Ref.21 Ref.68 Ref.69 Ref.79

Disulfide bond

624 ↔ 636

Ref.21 Ref.68 Ref.69 Ref.79

Cross-link

716

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.20

Cross-link

737

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.20

Cross-link

754

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.20

Cross-link

867

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.20

Cross-link

929

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.20

Cross-link

970

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.20

Natural variations

Alternative sequence

404 – 405

2

FL → LS in isoform 2.

VSP_002887

Alternative sequence

406 – 1210

805

Missing in isoform 2.

VSP_002888

Alternative sequence

628 – 705

78

CTGPG…QALLR → PGNESLKAMLFCLFKLSSCN QSNDGSVSHQSGSPAAQESC LGWIPSLLPSEFQLGWGGCS HLHAWPSASVIITASSCH in isoform 3.

VSP_002889

Alternative sequence

628

1

C → S in isoform 4.

VSP_002891

Alternative sequence

629 – 1210

582

Missing in isoform 4.

VSP_002892

Alternative sequence

706 – 1210

505

Missing in isoform 3.

VSP_002890

Natural variant

30 – 297

268

Missing Variant EGFR vIII; found in a lung cancer sample; somatic mutation; induces lung cancer when exogenously expressed.

VAR_066493

Natural variant

98

1

R → Q. Ref.7
Corresponds to variant rs17289589 [ dbSNP | Ensembl ].

VAR_019293

Natural variant

266

1

P → R. Ref.7
Corresponds to variant rs17336639 [ dbSNP | Ensembl ].

VAR_019294

Natural variant

521

1

R → K. Ref.7 Ref.83
Corresponds to variant rs2227983 [ dbSNP | Ensembl ].

VAR_019295

Natural variant

674

1

V → I Slightly increased autophosphorylation. Ref.7
Corresponds to variant rs17337079 [ dbSNP | Ensembl ].

VAR_019296

Natural variant

709

1

E → A Found in a lung cancer sample. Ref.81

VAR_026084

Natural variant

709

1

E → K Found in a lung cancer sample. Ref.81

VAR_026085

Natural variant

719

1

G → A Found in a lung cancer sample. Ref.81

VAR_026086

Natural variant

719

1

G → C Found in a lung cancer sample. Ref.81
Corresponds to variant rs28929495 [ dbSNP | Ensembl ].

VAR_026087

Natural variant

719

1

G → D Found in a lung cancer sample. Ref.81

VAR_026088

Natural variant

719

1

G → S Found in a lung cancer sample; somatic mutation; strongly increased kinase activity. Ref.73 Ref.80 Ref.81

VAR_019297

Natural variant

724

1

G → S Found in a lung cancer sample. Ref.81

VAR_026089

Natural variant

734

1

E → K Found in a lung cancer sample. Ref.81

VAR_026090

Natural variant

746 – 750

5

Missing Found in a lung cancer sample.

VAR_026092

Natural variant

746

1

Missing Found in a lung cancer sample.

VAR_026091

Natural variant

747 – 749

3

Missing Found in a lung cancer sample.

VAR_026094

Natural variant

747

1

L → F Found in a lung cancer sample. Ref.81

VAR_026093

Natural variant

748

1

R → P Found in a lung cancer sample. Ref.81

VAR_026095

Natural variant

752 – 759

8

Missing Found in a lung cancer sample.

VAR_026096

Natural variant

787

1

Q → R Found in a lung cancer sample. Ref.81

VAR_026097

Natural variant

790

1

T → M Found in a lung cancer sample; increased kinase activity. Ref.75 Ref.81

VAR_026098

Natural variant

833

1

L → V Found in a lung cancer sample. Ref.81

VAR_026099

Natural variant

834

1

V → L Found in a lung cancer sample. Ref.81

VAR_026100

Natural variant

858

1

L → M Found in a lung cancer sample. Ref.81

VAR_026101

Natural variant

858

1

L → R Found in a lung cancer sample; somatic mutation; constitutively activated enzyme with strongly increased kinase activity. Ref.73 Ref.80 Ref.81

VAR_019298

Natural variant

861

1

L → Q Found in a lung cancer sample. Ref.81

VAR_026102

Natural variant

873

1

G → E Found in a lung cancer sample. Ref.81

VAR_026103

Natural variant

962

1

R → G. Ref.7
Corresponds to variant rs17337451 [ dbSNP | Ensembl ].

VAR_019299

Natural variant

988

1

H → P. Ref.7
Corresponds to variant rs17290699 [ dbSNP | Ensembl ].

VAR_019300

Natural variant

1034

1

L → R. Ref.83
Corresponds to variant rs34352568 [ dbSNP | Ensembl ].

VAR_042095

Natural variant

1210

1

A → V. Ref.83
Corresponds to variant rs35918369 [ dbSNP | Ensembl ].

VAR_042096

Experimental info

Mutagenesis

275

1

Y → A: Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-309. Ref.68

Mutagenesis

287

1

F → A: Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-309. Ref.68

Mutagenesis

309

1

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. Ref.68

Mutagenesis

429

1

R → E: Abolishes autophosphorylation and activation of downstream kinases. Ref.68

Mutagenesis

587 – 590

4

DGPH → AGPA: Decreases intramolecular interactions and facilitates EGF binding. Ref.69

Mutagenesis

609

1

K → A: Decreases intramolecular interactions and facilitates EGF binding. Ref.69

Mutagenesis

688

1

L → A: Strongly reduced phosphorylation. Ref.76 Ref.77

Mutagenesis

689

1

V → A: Reduced autophosphorylation. Ref.77

Mutagenesis

689

1

V → M: Constitutively activated kinase. Ref.77

Mutagenesis

690

1

E → A: Reduced phosphorylation. Ref.76 Ref.77

Mutagenesis

692

1

L → A or P: Strongly reduced phosphorylation. Ref.76 Ref.77

Mutagenesis

693

1

T → A: Increased phosphorylation. Ref.77

Mutagenesis

693

1

T → D: Strongly reduced phosphorylation. Ref.77

Mutagenesis

694

1

P → A: Strongly reduced phosphorylation. Ref.77

Mutagenesis

699

1

P → A: Reduced phosphorylation. Ref.77

Mutagenesis

700

1

N → A: Abolishes phosphorylation. Ref.77

Mutagenesis

704

1

L → A: Abolishes phosphorylation. Ref.77

Mutagenesis

705

1

R → A: Abolishes phosphorylation. Ref.77

Mutagenesis

706

1

I → A: Abolishes phosphorylation. Ref.77

Mutagenesis

745

1

K → A or M: Abolishes kinase activity. Ref.77

Mutagenesis

974

1

D → A: Strongly reduced phosphorylation.

Mutagenesis

977

1

R → A: Reduced phosphorylation. Ref.76

Mutagenesis

1005 – 1006

2

ED → RK: Constitutively activated kinase.

Mutagenesis

1016

1

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. Ref.39

Mutagenesis

1092

1

Y → F: No change in interaction with PIK3C2B. Abolishes interaction with PIK3C2B; when associated with F-1197 and F-1016. Ref.39

Mutagenesis

1110

1

Y → F: No change in interaction with PIK3C2B. Ref.39

Mutagenesis

1172

1

Y → F: No change in interaction with PIK3C2B. Ref.39

Mutagenesis

1197

1

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. Ref.39

Sequence conflict

540

1

N → K in CAA25240. Ref.1

Secondary structure

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1210

Helix Strand Turn

Details...

Beta strand

40 – 43

4

Helix

44 – 55

12

Beta strand

59 – 63

5

Beta strand

65 – 67

3

Helix

77 – 81

5

Beta strand

84 – 87

4

Beta strand

89 – 93

5

Helix

101 – 103

3

Turn

114 – 116

3

Beta strand

117 – 122

6

Beta strand

145 – 152

8

Helix

159 – 161

3

Turn

164 – 167

4

Turn

173 – 175

3

Beta strand

195 – 197

3

Beta strand

200 – 202

3

Turn

203 – 205

3

Beta strand

211 – 215

5

Beta strand

224 – 229

6

Beta strand

236 – 238

3

Beta strand

241 – 247

7

Beta strand

249 – 256

8

Beta strand

259 – 263

5

Beta strand

267 – 271

5

Turn

272 – 275

4

Beta strand

276 – 279

4

Beta strand

285 – 287

3

Beta strand

290 – 294

5

Beta strand

299 – 301

3

Beta strand

305 – 309

5

Beta strand

321 – 323

3

Beta strand

330 – 332

3

Beta strand

340 – 342

3

Helix

343 – 345

3

Helix

353 – 355

3

Helix

357 – 359

3

Beta strand

363 – 367

5

Beta strand

369 – 371

3

Helix

373 – 377

5

Turn

380 – 383

4

Helix

389 – 397

9

Beta strand

400 – 403

4

Beta strand

405 – 408

4

Helix

418 – 420

3

Turn

433 – 435

3

Beta strand

436 – 442

7

Beta strand

458 – 464

7

Helix

472 – 474

3

Helix

477 – 480

4

Beta strand

492 – 494

3

Helix

496 – 498

3

Turn

499 – 503

5

Turn

507 – 509

3

Beta strand

515 – 519

5

Beta strand

522 – 525

4

Beta strand

540 – 543

4

Beta strand

548 – 557

10

Beta strand

571 – 575

5

Beta strand

579 – 587

9

Beta strand

590 – 594

5

Beta strand

597 – 600

4

Beta strand

602 – 611

10

Beta strand

616 – 619

4

Beta strand

629 – 632

4

Turn

633 – 635

3

Beta strand

704 – 706

3

Turn

709 – 711

3

Beta strand

712 – 720

9

Beta strand

722 – 731

10

Beta strand

740 – 747

8

Helix

756 – 768

13

Beta strand

777 – 791

15

Helix

798 – 804

7

Beta strand

806 – 808

3

Helix

811 – 830

20

Helix

840 – 842

3

Beta strand

843 – 847

5

Beta strand

850 – 853

4

Helix

858 – 861

4

Turn

862 – 865

4

Turn

878 – 880

3

Helix

883 – 888

6

Helix

893 – 908

16

Turn

914 – 917

4

Helix

920 – 922

3

Helix

923 – 929

7

Helix

941 – 950

10

Helix

955 – 957

3

Helix

961 – 973

13

Helix

975 – 978

4

Turn

982 – 986

5

Helix

996 – 1002

7

Helix

1013 – 1016

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (p170) [UniParc]. Last modified November 1, 1997. Version 2. Checksum: D8A2A50B4EFB6ED2	FASTA	1,210	134,277
	10 20 30 40 50 60 MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV 70 80 90 100 110 120 VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA 130 140 150 160 170 180 VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF 190 200 210 220 230 240 QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC 250 260 270 280 290 300 TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV 310 320 330 340 350 360 VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK 370 380 390 400 410 420 NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF 430 440 450 460 470 480 ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL 490 500 510 520 530 540 FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN 550 560 570 580 590 600 LLEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM 610 620 630 640 650 660 GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCPTNG PKIPSIATGM VGALLLLLVV 670 680 690 700 710 720 ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEAPN QALLRILKET EFKKIKVLGS 730 740 750 760 770 780 GAFGTVYKGL WIPEGEKVKI PVAIKELREA TSPKANKEIL DEAYVMASVD NPHVCRLLGI 790 800 810 820 830 840 CLTSTVQLIT QLMPFGCLLD YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA 850 860 870 880 890 900 RNVLVKTPQH VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY 910 920 930 940 950 960 GVTVWELMTF GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC WMIDADSRPK 970 980 990 1000 1010 1020 FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA LMDEEDMDDV VDADEYLIPQ 1030 1040 1050 1060 1070 1080 QGFFSSPSTS RTPLLSSLSA TSNNSTVACI DRNGLQSCPI KEDSFLQRYS SDPTGALTED 1090 1100 1110 1120 1130 1140 SIDDTFLPVP EYINQSVPKR PAGSVQNPVY HNQPLNPAPS RDPHYQDPHS TAVGNPEYLN 1150 1160 1170 1180 1190 1200 TVQPTCVNST FDSPAHWAQK GSHQISLDNP DYQQDFFPKE AKPNGIFKGS TAENAEYLRV 1210 APQSSEFIGA
	Isoform 2 (p60) (Truncated) (TEGFR) [UniParc]. Checksum: F5DEB31787EF1822	FASTA	405	44,664
	10 20 30 40 50 60 MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV 70 80 90 100 110 120 VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA 130 140 150 160 170 180 VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF 190 200 210 220 230 240 QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC 250 260 270 280 290 300 TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV 310 320 330 340 350 360 VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK 370 380 390 400 NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGLS
	Isoform 3 (p110) [UniParc]. Checksum: 4CF149492FF1650C	FASTA	705	77,312
	10 20 30 40 50 60 MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV 70 80 90 100 110 120 VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA 130 140 150 160 170 180 VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF 190 200 210 220 230 240 QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC 250 260 270 280 290 300 TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV 310 320 330 340 350 360 VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK 370 380 390 400 410 420 NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF 430 440 450 460 470 480 ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL 490 500 510 520 530 540 FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN 550 560 570 580 590 600 LLEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM 610 620 630 640 650 660 GENNTLVWKY ADAGHVCHLC HPNCTYGPGN ESLKAMLFCL FKLSSCNQSN DGSVSHQSGS 670 680 690 700 PAAQESCLGW IPSLLPSEFQ LGWGGCSHLH AWPSASVIIT ASSCH
	Isoform 4 [UniParc]. Checksum: 3A00A5511A3B6AE2	FASTA	628	69,228
	10 20 30 40 50 60 MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV 70 80 90 100 110 120 VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA 130 140 150 160 170 180 VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF 190 200 210 220 230 240 QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC 250 260 270 280 290 300 TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV 310 320 330 340 350 360 VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK 370 380 390 400 410 420 NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF 430 440 450 460 470 480 ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL 490 500 510 520 530 540 FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN 550 560 570 580 590 600 LLEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM 610 620 GENNTLVWKY ADAGHVCHLC HPNCTYGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells." Ullrich A., Coussens L., Hayflick J.S., Dull T.J., Gray A., Tam A.W., Lee J., Yarden Y., Libermann T.A., Schlessinger J., Downward J., Mayes E.L.V., Whittle N., Waterfield M.D., Seeburg P.H. Nature 309:418-425(1984) [PubMed: 6328312] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Possible role of variant RNA transcripts in the regulation of epidermal growth factor receptor expression in human placenta." Ilekis J.V., Stark B.C., Scoccia B. Mol. Reprod. Dev. 41:149-156(1995) [PubMed: 7654368] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Placenta.
[3]	"A 1.8 kb alternative transcript from the human epidermal growth factor receptor gene encodes a truncated form of the receptor." Reiter J.L., Maihle N.J. Nucleic Acids Res. 24:4050-4056(1996) [PubMed: 8918811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2). Tissue: Placenta.
[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: 9103388] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Placenta.
[5]	"Comparative genomic sequence analysis and isolation of human and mouse alternative EGFR transcripts encoding truncated receptor isoforms." Reiter J.L., Threadgill D.W., Eley G.D., Strunk K.E., Danielsen A.J., Schehl Sinclair C., Pearsall R.S., Green P.J., Yee D., Lampland A.L., Balasubramaniam S., Crossley T.D., Magnuson T.R., James C.D., Maihle N.J. Genomics 71:1-20(2001) [PubMed: 11161793] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 3 AND 4). Tissue: Placenta.
[6]	"Cloning of the cDNA for a short EGF receptor from human placenta." Xu L., Hong A., He X. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[7]	NIEHS SNPs program Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-98; ARG-266; LYS-521; ILE-674; GLY-962 AND PRO-988.
[8]	"Human and mouse alternative EGFR transcripts encoding only the extracellular domain of the receptor." Reiter J.L., Threadgill D.W., Danielsen A.J., Schehl C.M., Lampland A.L., Balasubramaniam S., Crossley T.O., Magnuson T.R., Maihle N.J. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 575-687.
[9]	"Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells." Lin C.R., Chen W.S., Kruiger W., Stolarsky L.S., Weber W., Evans R.M., Verma I.M., Gill G.N., Rosenfeld M.G. Science 224:843-848(1984) [PubMed: 6326261] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 713-924.
[10]	"Human epidermal growth factor receptor cDNA is homologous to a variety of RNAs overproduced in A431 carcinoma cells." Xu Y.H., Ishii S., Clark A.J.L., Sullivan M., Wilson R.K., Ma D.P., Roe B.A., Merlino G.T., Pastan I. Nature 309:806-810(1984) [PubMed: 6330563] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 150-962.
[11]	"Isolation of an evolutionarily conserved epidermal growth factor receptor cDNA from human A431 carcinoma cells." Simmen F.A., Gope M.L., Schulz T.Z., Wright D.A., Carpenter G., O'Malley B.W. Biochem. Biophys. Res. Commun. 124:125-132(1984) [PubMed: 6093780] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1028-1210.
[12]	"The human EGF receptor gene: structure of the 110 kb locus and identification of sequences regulating its transcription." Haley J.D., Whittle N., Bennett P., Kinchington D., Ullrich A., Waterfield M.D. Oncogene Res. 1:375-396(1987) [PubMed: 3329716] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29.
[13]	"Contributory effects of de novo transcription and premature transcript termination in the regulation of human epidermal growth factor receptor proto-oncogene RNA synthesis." Haley J.D., Waterfield M.D. J. Biol. Chem. 266:1746-1753(1991) [PubMed: 1988448] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29.
[14]	"Characterization and sequence of the promoter region of the human epidermal growth factor receptor gene." Ishii S., Xu Y.H., Stratton R.H., Roe B.A., Merlino G.T., Pastan I. Proc. Natl. Acad. Sci. U.S.A. 82:4920-4924(1985) [PubMed: 2991899] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29.
[15]	"Production of an epidermal growth factor receptor-related protein." Weber W., Gill G.N., Spiess J. Science 224:294-297(1984) [PubMed: 6324343] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 25-49.
[16]	Kohda D. Submitted (SEP-1997) to UniProtKB Cited for: PROTEIN SEQUENCE OF 540.
[17]	"Epidermal growth factor receptor threonine and serine residues phosphorylated in vivo." Heisermann G.J., Gill G.N. J. Biol. Chem. 263:13152-13158(1988) [PubMed: 3138233] [Abstract] Cited for: PROTEIN SEQUENCE OF 687-705; 986-998; 1000-1023; 1026-1030 AND 1068-1077, PHOSPHORYLATION AT THR-693; SER-695; SER-1070 AND SER-1071.
[18]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-39.
[19]	"Identification of residues in the nucleotide binding site of the epidermal growth factor receptor/kinase." Russo M.W., Lukas T.J., Cohen S., Staros J.V. J. Biol. Chem. 260:5205-5208(1985) [PubMed: 2985580] [Abstract] Cited for: PROTEIN SEQUENCE OF 740-744 AND 746-747.
[20]	"Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain." Huang F., Kirkpatrick D., Jiang X., Gygi S.P., Sorkin A. Mol. Cell 21:737-748(2006) [PubMed: 16543144] [Abstract] Cited for: PROTEIN SEQUENCE OF 861-875 AND 914-932, UBIQUITINATION AT LYS-716; LYS-737; LYS-754; LYS-867; LYS-929 AND LYS-970, MASS SPECTROMETRY.
[21]	"Disulfide bond structure of human epidermal growth factor receptor." Abe Y., Odaka M., Inagaki F., Lax I., Schlessinger J., Kohda D. J. Biol. Chem. 273:11150-11157(1998) [PubMed: 9556602] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS.
[22]	"ATP-stimulated interaction between epidermal growth factor receptor and supercoiled DNA." Mroczkowski B., Mosig G., Cohen S. Nature 309:270-273(1984) [PubMed: 6325948] [Abstract] Cited for: RECEPTOR ACTIVITY.
[23]	"Receptors for epidermal growth factor and other polypeptide mitogens." Carpenter G. Annu. Rev. Biochem. 56:881-914(1987) [PubMed: 3039909] [Abstract] Cited for: REVIEW.
[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: 2790960] [Abstract] Cited for: LIGAND-BINDING.
[25]	"All autophosphorylation sites of epidermal growth factor (EGF) receptor and HER2/neu are located in their carboxyl-terminal tails. Identification of a novel site in EGF receptor." Margolis B.L., Lax I., Kris R., Dombalagian M., Honegger A.M., Howk R., Givol D., Ullrich A., Schlessinger J. J. Biol. Chem. 264:10667-10671(1989) [PubMed: 2543678] [Abstract] Cited for: AUTOPHOSPHORYLATION AT TYR-1110.
[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: 7679104] [Abstract] Cited for: IDENTIFICATION OF AMPHIREGULIN AS LIGAND.
[27]	"Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor." Bagowski C.P., Stein-Gerlach M., Choidas A., Ullrich A. EMBO J. 18:5567-5576(1999) [PubMed: 10523301] [Abstract] Cited for: PHOSPHORYLATION AT THR-678 AND THR-693.
[28]	"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: 8144591] [Abstract] Cited for: IDENTIFICATION OF BETACELLULIN/BTC AS LIGAND.
[29]	"Tyrosine phosphorylation of the c-cbl proto-oncogene protein product and association with epidermal growth factor (EGF) receptor upon EGF stimulation." Galisteo M.L., Dikic I., Batzer A.G., Langdon W.Y., Schlessinger J. J. Biol. Chem. 270:20242-20245(1995) [PubMed: 7657591] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CBL, INTERACTION WITH CBL.
[30]	"Analysis of the glycosylation patterns of the extracellular domain of the epidermal growth factor receptor expressed in Chinese hamster ovary fibroblasts." Smith K.D., Davies M.J., Bailey D., Renouf D.V., Hounsell E.F. Growth Factors 13:121-132(1996) [PubMed: 8962717] [Abstract] Cited for: GLYCOSYLATION AT ASN-128; ASN-175; ASN-413; ASN-444 AND ASN-528.
[31]	"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: 9419975] [Abstract] Cited for: IDENTIFICATION OF EPIREGULIN/EREG AS LIGAND.
[32]	"Inhibition of the receptor-binding function of clathrin adaptor protein AP-2 by dominant-negative mutant mu2 subunit and its effects on endocytosis." Nesterov A., Carter R.E., Sorkina T., Gill G.N., Sorkin A. EMBO J. 18:2489-2499(1999) [PubMed: 10228163] [Abstract] Cited for: INTERACTION WITH AP2M1.
[33]	"Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck." Braverman L.E., Quilliam L.A. J. Biol. Chem. 274:5542-5549(1999) [PubMed: 10026169] [Abstract] Cited for: INTERACTION WITH GRB2; NCK1 AND NCK2.
[34]	"Characterization of the N-oligosaccharides attached to the atypical Asn-X-Cys sequence of recombinant human epidermal growth factor receptor." Sato C., Kim J.-H., Abe Y., Saito K., Yokoyama S., Kohda D. J. Biochem. 127:65-72(2000) [PubMed: 10731668] [Abstract] Cited for: GLYCOSYLATION AT ASN-56; ASN-352; ASN-361; ASN-568 AND ASN-603.
[35]	"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: 11602604] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RGS16.
[36]	"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: 12873986] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION, INTERACTION WITH STAT3, PHOSPHORYLATION AT TYR-1092 AND TYR-1110.
[37]	"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: 15282549] [Abstract] Cited for: ENZYME REGULATION, INTERACTION WITH LRIG1.
[38]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[39]	"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: 10805725] [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.
[40]	"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: 11116146] [Abstract] Cited for: FUNCTION IN NF-KAPPA-B ACTIVATION, INTERACTION WITH RIPK1.
[41]	"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: 11483589] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MUC1, INTERACTION WITH MUC1.
[42]	"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: 15590694] [Abstract] Cited for: ENZYME REGULATION, INTERACTION WITH SOCS5.
[43]	"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: 15611079] [Abstract] Cited for: IDENTIFICATION OF EPIGEN/EPGN AS A LIGAND.
[44]	"Extended Range Proteomic Analysis (ERPA): a new and sensitive LC-MS platform for high sequence coverage of complex proteins with extensive post-translational modifications-comprehensive analysis of beta-casein and epidermal growth factor receptor (EGFR)." Wu S.L., Kim J., Hancock W.S., Karger B. J. Proteome Res. 4:1155-1170(2005) [PubMed: 16083266] [Abstract] Cited for: GLYCOSYLATION AT ASN-56; ASN-128; ASN-175; ASN-196; ASN-352; ASN-361; ASN-413; ASN-444; ASN-528; ASN-568 AND ASN-603, PHOSPHORYLATION AT THR-693; SER-991 AND SER-1026, MASS SPECTROMETRY.
[45]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-998; TYR-1069; TYR-1092; SER-1166 AND TYR-1172, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[46]	"Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC." Gevaert K., Staes A., Van Damme J., De Groot S., Hugelier K., Demol H., Martens L., Goethals M., Vandekerckhove J. Proteomics 5:3589-3599(2005) [PubMed: 16097034] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-978, MASS SPECTROMETRY. Tissue: Hepatoma.
[47]	"Functional implications of altered subcellular localization of PELP1 in breast cancer cells." Vadlamudi R.K., Manavathi B., Balasenthil S., Nair S.S., Yang Z., Sahin A.A., Kumar R. Cancer Res. 65:7724-7732(2005) [PubMed: 16140940] [Abstract] Cited for: INTERACTION WITH PELP1.
[48]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693; SER-991; SER-995; TYR-998; SER-1064; TYR-1069; TYR-1092; TYR-1110; TYR-1138; TYR-1172 AND TYR-1197, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[49]	"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: 17115032] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION, FUNCTION IN PCNA PHOSPHORYLATION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION.
[50]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-869; TYR-1092; TYR-1172 AND TYR-1197, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[51]	"Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia." Groenestege W.M.T., Thebault S., van der Wijst J., van den Berg D., Janssen R., Tejpar S., van den Heuvel L.P., van Cutsem E., Hoenderop J.G., Knoers N.V., Bindels R.J. J. Clin. Invest. 117:2260-2267(2007) [PubMed: 17671655] [Abstract] Cited for: TISSUE SPECIFICITY.
[52]	"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: 17182860] [Abstract] Cited for: INTERACTION WITH TNF2, SUBCELLULAR LOCATION.
[53]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[54]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-991; TYR-998; SER-1166; TYR-1069; TYR-1172 AND TYR-1197, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[55]	"Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein." Brummer T., Larance M., Herrera Abreu M.T., Lyons R.J., Timpson P., Emmerich C.H., Fleuren E.D.G., Lehrbach G.M., Schramek D., Guilhaus M., James D.E., Daly R.J. EMBO J. 27:2305-2316(2008) [PubMed: 19172738] [Abstract] Cited for: INTERACTION WITH GAB2.
[56]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693 AND SER-991, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[57]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693; SER-695; THR-725; SER-991; SER-1025; SER-1026; SER-1037; SER-1039; SER-1042; SER-1064; SER-1081; SER-1166 AND TYR-1197, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[58]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693; SER-695; SER-991; THR-993; SER-995; TYR-998; SER-1039; THR-1041; SER-1042; SER-1045; SER-1064 AND SER-1166, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[59]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[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: 19836242] [Abstract] Cited for: ENZYME REGULATION BY PTPRJ AND PTPRK, PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRJ, SUBCELLULAR LOCATION, INTERACTION WITH CBL AND GRB2.
[61]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-352; ASN-413 AND ASN-568, MASS SPECTROMETRY. Tissue: Liver.
[62]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-998; TYR-1016; TYR-1092; TYR-1110; TYR-1138; TYR-1172 AND TYR-1197, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[63]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-693, MASS SPECTROMETRY.
[64]	"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: 20674546] [Abstract] Cited for: INTERACTION WITH COPG, SUBCELLULAR LOCATION, TOPOLOGY.
[65]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[66]	"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: 21258366] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION AND CELL MIGRATION, METHYLATION AT ARG-1199 BY PRMT5, INTERACTION WITH PRMT5 AND PTPN6.
[67]	"FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-kappaB." Guo C., Stark G.R. Proc. Natl. Acad. Sci. U.S.A. 108:7968-7973(2011) [PubMed: 21518868] [Abstract] Cited for: INTERACTION WITH FER, PHOSPHORYLATION.
[68]	"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: 12297050] [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.
[69]	"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: 12620237] [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.
[70]	"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: 15374980] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 695-1022 IN COMPLEX WITH GW572016, CATALYTIC ACTIVITY, FUNCTION.
[71]	"Structural basis for inhibition of the epidermal growth factor receptor by cetuximab." Li S., Schmitz K.R., Jeffrey P.D., Wiltzius J.J., Kussie P., Ferguson K.M. Cancer Cell 7:301-311(2005) [PubMed: 15837620] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 25-642 IN COMPLEX WITH CETUXIMAB.
[72]	"A structural model for the membrane-bound form of the juxtamembrane domain of the epidermal growth factor receptor." Choowongkomon K., Carlin C.R., Sonnichsen F.D. J. Biol. Chem. 280:24043-24052(2005) [PubMed: 15840573] [Abstract] Cited for: STRUCTURE BY NMR OF 669-721.
[73]	"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: 17349580] [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.
[74]	"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: 18046415] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 702-1022 IN COMPLEX WITH ERRFI1, ENZYME REGULATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, INTERACTION WITH ERRFI1.
[75]	"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: 18227510] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 695-1022 OF VARIANT MET-790, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT MET-790.
[76]	"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: 19563760] [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.
[77]	"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: 19560417] [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.
[78]	"Spatial structure of the transmembrane domain heterodimer of ErbB1 and ErbB2 receptor tyrosine kinases." Mineev K.S., Bocharov E.V., Pustovalova Y.E., Bocharova O.V., Chupin V.V., Arseniev A.S. J. Mol. Biol. 400:231-243(2010) [PubMed: 20471394] [Abstract] Cited for: STRUCTURE BY NMR OF 634-677 IN COMPLEX WITH ERBB2, SUBUNIT.
[79]	"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: 20837704] [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.
[80]	"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: 15118125] [Abstract] Cited for: VARIANTS SER-719 AND ARG-858, POSSIBLE INVOLVEMENT IN LUNG CANCER.
[81]	"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: 16533793] [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.
[82]	"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: 16672372] [Abstract] Cited for: VARIANT 30-VAL--ARG-297 DEL, POSSIBLE INVOLVEMENT IN LUNG CANCER.
[83]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-521; ARG-1034 AND VAL-1210.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Wikipedia

EGFR entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00588 mRNA. Translation: CAA25240.1.
U95089 mRNA. Translation: AAB53063.1.
U48722 mRNA. Translation: AAC50802.1.
U48723 Genomic DNA. Translation: AAC50804.1.
U48724 Genomic DNA. Translation: AAC50796.1.
U48725 Genomic DNA. Translation: AAC50797.1.
U48726 Genomic DNA. Translation: AAC50798.1.
U48727 Genomic DNA. Translation: AAC50799.1.
U48728 Genomic DNA. Translation: AAC50800.1.
U48729 Genomic DNA. Translation: AAC50801.1.
AF288738 Genomic DNA. Translation: AAG35786.1.
AF288738 Genomic DNA. Translation: AAG35787.1.
AF288738 Genomic DNA. Translation: AAG35788.1.
AF288738 Genomic DNA. Translation: AAG35789.1.
AF288738 Genomic DNA. Translation: AAG35790.1.
AY698024 mRNA. Translation: AAT97979.1.
AY588246 Genomic DNA. Translation: AAS83109.1.
AF277897 mRNA. Translation: AAK01080.1.
AF125253 mRNA. Translation: AAG43240.1.
AF125539, AF125538 Genomic DNA. Translation: AAG43243.1.
X06370 Genomic DNA. Translation: CAA29668.1.
X00663 mRNA. Translation: CAA25282.1.
M38425 Genomic DNA. Translation: AAA63171.1.
M11234 Genomic DNA. Translation: AAA52370.1.

IPI

IPI00018274.
IPI00221346.
IPI00221347.
IPI00221348.

PIR

GQHUE. A00641.

RefSeq

NP_005219.2. NM_005228.3.
NP_958439.1. NM_201282.1.
NP_958440.1. NM_201283.1.
NP_958441.1. NM_201284.1.

UniGene

Hs.488293.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DNQ	model	-	A	25-336	[»]
1DNR	model	-	A	337-645	[»]
1IVO	X-ray	3.30	A/B	25-646	[»]
1M14	X-ray	2.60	A	695-1022	[»]
1M17	X-ray	2.60	A	695-1022	[»]
1MOX	X-ray	2.50	A/B	25-525	[»]
1NQL	X-ray	2.80	A	25-642	[»]
1XKK	X-ray	2.40	A	695-1022	[»]
1YY9	X-ray	2.60	A	25-642	[»]
1Z9I	NMR	-	A	669-721	[»]
2EB2	X-ray	2.50	A	695-1022	[»]
2EB3	X-ray	2.84	A	695-1022	[»]
2EXP	model	-	A	311-326	[»]
2EXQ	model	-	A	27-536	[»]
2GS2	X-ray	2.80	A	696-1022	[»]
2GS6	X-ray	2.60	A	696-1022	[»]
2GS7	X-ray	2.60	A/B	696-1022	[»]
2ITN	X-ray	2.47	A	696-1019	[»]
2ITO	X-ray	3.25	A	696-1022	[»]
2ITP	X-ray	2.74	A	696-1022	[»]
2ITQ	X-ray	2.68	A	696-1022	[»]
2ITT	X-ray	2.73	A	696-1022	[»]
2ITU	X-ray	2.80	A	696-1022	[»]
2ITV	X-ray	2.47	A	696-1022	[»]
2ITW	X-ray	2.88	A	696-1022	[»]
2ITX	X-ray	2.98	A	696-1022	[»]
2ITY	X-ray	3.42	A	696-1022	[»]
2ITZ	X-ray	2.72	A	696-1022	[»]
2J5E	X-ray	3.10	A	696-1022	[»]
2J5F	X-ray	3.00	A	696-1022	[»]
2J6M	X-ray	3.10	A	696-1022	[»]
2JIT	X-ray	3.10	A/B	696-1022	[»]
2JIU	X-ray	3.05	A/B	695-1022	[»]
2JIV	X-ray	3.50	A/B	695-1022	[»]
2KS1	NMR	-	B	634-677	[»]
2RF9	X-ray	3.50	A/B	696-1022	[»]
2RFD	X-ray	3.60	A/B	702-1022	[»]
2RFE	X-ray	2.90	A/B/C/D	702-1022	[»]
2RGP	X-ray	2.00	A	702-1016	[»]
3B2U	X-ray	2.58	A/B/E/I/M/P/S/V	335-538	[»]
3B2V	X-ray	3.30	A	25-642	[»]
3BEL	X-ray	2.30	A	702-1016	[»]
3BUO	X-ray	2.60	A/C	1063-1075	[»]
3C09	X-ray	3.20	A/D	335-538	[»]
3G5V	X-ray	2.00	C	311-326	[»]
3G5Y	X-ray	1.59	E	311-326	[»]
3GOP	X-ray	2.80	A	669-1022	[»]
3GT8	X-ray	2.96	A/B/C/D	696-1022	[»]
3IKA	X-ray	2.90	A/B	694-1022	[»]
3LZB	X-ray	2.70	A/B/C/D/E/F/G/H	696-983	[»]
3NJP	X-ray	3.30	A/B	25-638	[»]
3OB2	X-ray	2.10	A	1063-1074	[»]
3OP0	X-ray	2.52	C/D	1066-1076	[»]
3P0Y	X-ray	1.80	A	334-538	[»]
3PFV	X-ray	2.27	C/D	1066-1076	[»]
3POZ	X-ray	1.50	A	696-1022	[»]

ProteinModelPortal

P00533.

SMR

P00533. Positions 26-1003.

DisProt

DP00309.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-405N.
DIP-5764N.

IntAct

P00533. 205 interactions.

MINT

MINT-206389.

STRING

P00533.

PTM databases

GlycoSuiteDB

P00533.

PhosphoSite

P00533.

Polymorphism databases

DMDM

2811086.

2D gel databases

SWISS-2DPAGE

P00533.

Proteomic databases

PeptideAtlas

P00533.

PRIDE

P00533.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000275493; ENSP00000275493; ENSG00000146648.

GeneID

1956.

KEGG

hsa:1956.

UCSC

uc003tqi.1. human.
uc003tqj.1. human.
uc003tqk.1. human.

Organism-specific databases

CTD

1956.

GeneCards

GC07P055054.

H-InvDB

HIX0025338.

HGNC

HGNC:3236. EGFR.

HPA

CAB000035.
HPA001200.
HPA018530.

MIM

131550. gene.
211980. phenotype.

neXtProt

NX_P00533.

Orphanet

360. Glioblastoma.

PharmGKB

PA7360.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG000490.

InParanoid

P00533.

OMA

MRRRHIV.

PhylomeDB

P00533.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
arf6cyclingpathway. Arf6 signaling events.
endothelinpathway. Endothelins.
lysophospholipid_pathway. LPA receptor mediated events.
telomerasepathway. Regulation of Telomerase.
ptp1bpathway. Signaling events mediated by PTP1B.
syndecan_3_pathway. Syndecan-3-mediated signaling events.
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P00533.

Bgee

P00533.

Genevestigator

P00533.

GermOnline

ENSG00000146648. Homo sapiens.

Family and domain databases

InterPro

IPR000494. EGF_rcpt_L.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
[Graphical view]

KO

K04361.

Pfam

PF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]

PIRSF

PIRSF000619. TyrPK_EGF-R. 1 hit.

PRINTS

PR00109. TYRKINASE.

SMART

SM00261. FU. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF57184. Grow_fac_recept. 2 hits.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00002. Cetuximab.
DB00530. Erlotinib.
DB00317. Gefitinib.
DB01259. Lapatinib.
DB00281. Lidocaine.
DB01269. Panitumumab.
DB00072. Trastuzumab.

NextBio

7931.

PMAP-CutDB

P00533.

SOURCE

Search...

Entry information

Entry name

EGFR_HUMAN

Accession

Primary (citable) accession number: P00533
Secondary accession number(s): O00688 , O00732, P06268, Q14225, Q68GS5, Q92795, Q9BZS2, Q9GZX1, Q9H2C9, Q9H3C9, Q9UMD7, Q9UMD8, Q9UMG5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 179 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.