EGFR_HUMAN » Epidermal growth factor receptor

EGFR_HUMAN » Epidermal growth factor receptor
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
EGFR_HUMAN » Epidermal growth factor receptor » Proto-oncogene c-ErbB-1;Receptor tyrosine-protein kinase erbB-1;
Hydrophobic Thickness 31.6 ± 1.4 Å
Tilt Angle 0 ± 0°
ΔGtransfer -43.0 kcal/mol
ΔGfold -22.2 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome, HMDB
Topology Out
TM Segments 646-669 (644-671)
Pathways

Adherens junction (KEGG)

Bladder cancer (KEGG)

Calcium signaling pathway (KEGG)

Cytokine-cytokine receptor interaction (KEGG)

Developmental Biology (Reactome)

Dorso-ventral axis formation (KEGG)

Endocytosis (KEGG)

Endometrial cancer (KEGG)

Epithelial cell signaling in Helicobacter pylori infection (KEGG)

ErbB signaling pathway (KEGG)

Estrogen signaling pathway (KEGG)

Focal adhesion (KEGG)

Gap junction (KEGG)

Glioma (KEGG)

GnRH signaling pathway (KEGG)

Hepatitis C (KEGG)

HIF-1 signaling pathway (KEGG)

Immune System (Reactome)

MAPK signaling pathway (KEGG)

MAPK signaling pathway - fly (KEGG)

Melanoma (KEGG)

Non-small cell lung cancer (KEGG)

Pancreatic cancer (KEGG)

Pathways in cancer (KEGG)

Phosphatidylinositol Phosphate Metabolism (SMPDB)

PI3K-Akt signaling pathway (KEGG)

Prostate cancer (KEGG)

Proteoglycans in cancer (KEGG)

Regulation of actin cytoskeleton (KEGG)

Signal Transduction (Reactome)

PDB 1z9i (669-721), 4lqm (694-1022), 4lrm (694-1022), 1m14 (695-1022), 1m17 (695-1022), 1xkk (695-1022), 2jiu (695-1022), 2jiv (695-1022), 4i1z (695-1022), 4i20 (695-1022), 4i23 (695-1022), 4rj4 (695-1022), 4rj5 (695-1022), 4rj6 (695-1022), 4rj7 (695-1022), 4rj8 (695-1022), 4tks (695-1022), 2itn (696-1019), 2ito (696-1022), 2itp (696-1022), 2itq (696-1022), 2itt (696-1022), 2itu (696-1022), 2itv (696-1022), 2itw (696-1022), 2itx (696-1022), 2ity (696-1022), 2itz (696-1022), 2j5e (696-1022), 2j5f (696-1022), 2j6m (696-1022), 2jit (696-1022), 3poz (696-1022), 3w2s (696-1022), 3w32 (696-1022), 3w33 (696-1022), 4hjo (696-1022), 4r5s (696-1022), 4wkq (696-1022), 4wrg (696-1022), 3lzb (696-983), 3w2o (698-1022), 3w2p (698-1022), 3w2q (698-1022), 3w2r (698-1022), 2rgp (702-1016), 3bel (702-1016), 3b2u (A/B...=335-538), 3gt8 (A/B/C/D=696-1022), 2rfe (A/B/C/D=702-1022), 1mox (A/B=25-525), 3njp (A/B=25-638), 1ivo (A/B=25-646), 2m0b (A/B=634-677), 2m20 (A/B=642-697), 3ika (A/B=694-1022), 4ll0 (A/B=694-1022), 4i21 (A/B=695-1022), 4i24 (A/B=695-1022), 2gs7 (A/B=696-1022), 2rf9 (A/B=696-1022), 4g5p (A/B=696-1022), 2rfd (A/B=702-1022), 4krm (A/C...=335-538), 3buo (A/C=1063-1075), 3c09 (A/D=336-538), 3qwq (A=1-642), 3ob2 (A=1063-1074), 1nql (A=25-642), 1yy9 (A=25-642), 3b2v (A=25-642), 4kro (A=25-642), 4krp (A=25-642), 3p0y (A=334-538), 4krl (A=335-538), 3gop (A=669-1022), 2eb2 (A=695-1022), 2eb3 (A=695-1022), 3ug1 (A=695-1022), 3ug2 (A=695-1022), 3vjn (A=695-1022), 3vjo (A=695-1022), 4i22 (A=695-1022), 4li5 (A=696-1020), 4jq7 (A=696-1021), 4jq8 (A=696-1021), 4jr3 (A=696-1021), 4jrv (A=696-1021), 2gs2 (A=696-1022), 2gs6 (A=696-1022), 4g5j (A=696-1022), 4riw (B/D=682-1022), 4rix (B/D=682-1022), 4riy (B/D=682-1022), 3vrp (B=1062-1074), 2ks1 (B=634-677), 3op0 (C/D=1066-1076), 3pfv (C/D=1066-1076), 3vrr (C=1062-1074), 3g5v (C=311-326), 3g5y (E=311-326)
OPM 1z9i, 2ks1, 2m0b, 2m20
Complexes

EGFR:ERBB3_HUMAN

ERBB2:EGFR_HUMAN

TGFA:EGFR_HUMAN

EGF:EGFR_HUMAN

EGFR:EGFR_HUMAN

Interactions

1A02, Complex: 1A02:EGFR, PubMed

4F2, Complex: 4F2:EGFR, PubMed

A4, Complex: A4:EGFR, PubMed

ACSL3, Complex: EGFR:ACSL3, PubMed

ADCK3, Complex: EGFR:ADCK3

AL3A2, Complex: AL3A2:EGFR

AREG, Complex: AREG:EGFR, PubMed

AT1B1, Complex: AT1B1:EGFR, PubMed

ATAD1, Complex: ATAD1:EGFR

BTC, Complex: EGFR:BTC, PubMed

CADH1, Complex: CADH1:EGFR, PubMed

CADH5, Complex: CADH5:EGFR

CALX, Complex: CALX:EGFR, PubMed

CCD47, Complex: EGFR:CCD47

CD166, Complex: EGFR:CD166, PubMed

CD44, Complex: CD44:EGFR, PubMed

CDCP1, Complex: CDCP1:EGFR, PubMed

CEAM1, Complex: EGFR:CEAM1, PubMed

CEND, Complex: EGFR:CEND, PubMed

CKAP4, Complex: CKAP4:EGFR, PubMed

COHA1, Complex: COHA1:EGFR, PubMed

DCBD2, Complex: EGFR:DCBD2

DHB12, Complex: DHB12:EGFR

DHC24, Complex: DHC24:EGFR

DJB12, Complex: DJB12:EGFR

DJC11, Complex: DJC11:EGFR

DNJC4, Complex: DNJC4:EGFR, PubMed

DRS7B, Complex: DRS7B:EGFR

DSG2, Complex: DSG2:EGFR

EFNB1, Complex: EGFR:EFNB1, PubMed

EGFR, Complex: Homodimer of epidermal growth factor, PDBID: 2GS7

EGF, Complex: EGF:EGFR, PubMed

EGF, Complex: EGFR:EGF, PDBID: 1ivo

EMD, Complex: EGFR:EMD, PubMed

EPHA2, Complex: EPHA2:EGFR, PubMed

EPHB4, Complex: EGFR:EPHB4, PubMed

ERBB2, Complex: ERBB2:EGFR, PubMed

ERBB3, Complex: ERBB3:EGFR, PubMed

ERBB4, Complex: EGFR:ERBB4, PubMed

EREG, Complex: EGFR:EREG, PubMed

ESR1, Complex: ESR1:SRC:EGFR, PubMed

FACR1, Complex: FACR1:EGFR

FDFT, Complex: FDFT:EGFR

FKBP8, Complex: FKBP8:EGFR, PubMed

HBEGF, Complex: HBEGF:EGFR, PubMed

HUMMR, Complex: EGFR:HUMMR, PubMed

I17RD, Complex: EGFR:I17RD, PubMed

ICAM1, Complex: ICAM1:EGFR, PubMed

IGF1R, Complex: IGF1R:EGFR, PubMed

ILVBL, Complex: ILVBL:EGFR, PubMed

ITA5, Complex: ITA5:EGFR, PubMed

ITAV, Complex: ITAV:ITB3:EGFR

ITB2, Complex: EGFR:ITB2, PubMed

ITB4, Complex: ITB4:EGFR, PubMed

LAMP1, Complex: EGFR:LAMP1

LAT, Complex: LAT:EGFR, PubMed

LRC59, Complex: LRC59:EGFR, PubMed

LRIG1, Complex: EGFR:LRIG1, PubMed

LRP1, Complex: EGFR:LRP1, PubMed

LSR, Complex: LSR:EGFR

MET, Complex: MET:EGFR, PubMed

MMP14, Complex: EGFR:MMP14, PubMed

MUC1, Complex: EGFR:MUC1, PubMed

NCAM1, Complex: EGFR:NCAM1, PubMed

NCLN, Complex: EGFR:NCLN

NRG1, Complex: EGFR:NRG1, PubMed

NTRK2, Complex: EGFR:NTRK2, PubMed

PGFRA, Complex: EGFR:PGFRA, PubMed

PGFRB, Complex: PGFRB:EGFR, PubMed

PHAG1, Complex: PHAG1:EGFR

PLD3, Complex: EGFR:PLD3

PLPL2, Complex: EGFR:PLPL2, PubMed

PLS1, Complex: EGFR:PLS1, PubMed

PTN2, Complex: PTN2:EGFR, PubMed

PTPRB, Complex: EGFR:PTPRB, PubMed

PTPRC, Complex: EGFR:PTPRC, PubMed

PTPRD, Complex: PTPRD:EGFR, PubMed

PTPRF, Complex: PTPRF:EGFR, PubMed

PTPRJ, Complex: PTPRJ:EGFR, PubMed

PTPRS, Complex: EGFR:PTPRS, PubMed

RET, Complex: EGFR:RET, PubMed

ROR1, Complex: EGFR:ROR1, PubMed

ROS1, Complex: ROS1:EGFR, PubMed

RPN1, Complex: RPN1:EGFR

SC61B, Complex: EGFR:SC61B, PubMed

SE1L1, Complex: SE1L1:EGFR

SGPL1, Complex: EGFR:SGPL1, PubMed

SPTC1, Complex: SPTC1:EGFR

SRAC1, Complex: SRAC1:EGFR, PubMed

SRPRB, Complex: SRPRB:EGFR

SSRA, Complex: SSRA:EGFR, PubMed

SSRD, Complex: SSRD:EGFR

STX17, Complex: STX17:EGFR

SUSD1, Complex: SUSD1:EGFR, PubMed

TFR1, Complex: EGFR:TFR1

TGFA, Complex: EGFR:TGFA, PDBID: 1mox

TGFA, Complex: TGFA:EGFR, PubMed

TIM50, Complex: TIM50:EGFR

TLR2, Complex: TLR2:EGFR, PubMed

TLR4, Complex: TLR4:EGFR, PubMed

TNR1A, Complex: EGFR:TNR1A, PubMed

TNR6, Complex: TNR6:EGFR, PubMed

TOIP1, Complex: TOIP1:EGFR

TOM22, Complex: TOM22:EGFR

TR10B, Complex: EGFR:TR10B

VAPA, Complex: VAPA:EGFR, PubMed

Domains

AA: 57-168, PDBID: 1IVO, Subunit A, Seq Identity:100%, Receptor L domain

AA: 177-338, PDBID: 1IVO, Subunit A, Seq Identity:100%, Furin-like cysteine rich region

AA: 361-481, PDBID: 1IVO, Subunit A, Seq Identity:100%, Receptor L domain

AA: 505-637, PDBID: 1IVO, Subunit A, Seq Identity:100%, Growth factor receptor domain IV

AA: 712-968, PDBID: 1M14, Subunit A, Seq Identity:100%, Protein tyrosine kinase

UniProt annotation for EGFR_HUMAN » Epidermal growth factor receptor
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.

FUNCTION: Isoform 2 may act as an antagonist of EGF action.

CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

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.

SUBUNIT: 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, CBLB and CBLC; 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 COPG1; 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. Interacts with ATX2. Interacts with GAREM. Interacts (ubiquitinated) with ANKRD13A/B/D; the interaction is direct and may regulate EGFR internalization after EGF stimulation. Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts (via C-terminal cytoplasmic kinase domain) with ZPR1 (via zinc fingers). Interacts with RNF115 and RNF126.

TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers.

DISEASE: Lung cancer (LNCR) OMIM: 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. entry is involved in disease pathogenesis.

DISEASE: Inflammatory skin and bowel disease, neonatal, 2 (NISBD2) OMIM: A disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized. disease is caused by mutations affecting the gene represented in this entry.

UniProt features for EGFR_HUMAN » Epidermal growth factor receptor
SIGNAL 1 24
CHAIN 25 1210 Epidermal growth factor receptor.
REPEAT 75 300 Approximate.
REPEAT 390 600 Approximate.
DOMAIN 712 979 Protein kinase.
REGION 688 704 Important for dimerization, phosphorylation and activation.
ACT_SITE 837 837 Proton acceptor (By similarity).
SITE 1016 1016 Important for interaction with PIK3C2B.
DISULFID 31 58
DISULFID 157 187
DISULFID 190 199
DISULFID 194 207
DISULFID 215 223
DISULFID 219 231
DISULFID 232 240
DISULFID 236 248
DISULFID 251 260
DISULFID 264 291
DISULFID 295 307
DISULFID 311 326
DISULFID 329 333
DISULFID 337 362
DISULFID 470 499
DISULFID 506 515
DISULFID 510 523
DISULFID 526 535
DISULFID 539 555
DISULFID 558 571
DISULFID 562 579
DISULFID 582 591
DISULFID 595 617
DISULFID 620 628
DISULFID 624 636
CROSSLNK 716 716 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).
CROSSLNK 737 737 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).
CROSSLNK 754 754 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).
CROSSLNK 867 867 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).
CROSSLNK 929 929 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).
CROSSLNK 970 970 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).
Amino Acid Sequence for EGFR_HUMAN » Epidermal growth factor receptor
MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN LLEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCPTNG PKIPSIATGM VGALLLLLVV ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEAPN QALLRILKET EFKKIKVLGS GAFGTVYKGL WIPEGEKVKI PVAIKELREA TSPKANKEIL DEAYVMASVD NPHVCRLLGI CLTSTVQLIT QLMPFGCLLD YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA RNVLVKTPQH VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY GVTVWELMTF GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC WMIDADSRPK FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA LMDEEDMDDV VDADEYLIPQ QGFFSSPSTS RTPLLSSLSA TSNNSTVACI DRNGLQSCPI KEDSFLQRYS SDPTGALTED SIDDTFLPVP EYINQSVPKR PAGSVQNPVY HNQPLNPAPS RDPHYQDPHS TAVGNPEYLN TVQPTCVNST FDSPAHWAQK GSHQISLDNP DYQQDFFPKE AKPNGIFKGS TAENAEYLRV APQSSEFIGA