Names & Taxonomy

Uniprot ID:
P00533
Entry Name:
EGFR_HUMAN
Status:
reviewed
Protein Names:
Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1)
Gene Names:
EGFR ERBB ERBB1 HER1
Gene Names Primary:
EGFR
Organism:
Homo sapiens (Human)

Structure

Length:
1210
Sequence:
MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLNTVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRVAPQSSEFIGA
Proteomes:
UP000005640

Subcellular location

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. Nucleus. Note=In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand. Colocalized with GPER1 in the nucleus of estrogen agonist-induced cancer-associated fibroblasts (CAF).; Isoform 2: Secreted.

Function

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.; Isoform 2 may act as an antagonist of EGF action.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
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.
Active Site:
ACT_SITE 837 837 Proton acceptor.
Cross Reference Drug Bank:
DB08916 DB00002 DB00530 DB00317 DB01259 DB00281 DB09559 DB09330 DB01269 DB00072 DB05294
Gene Ontology Go:
basolateral plasma membrane
cell surface
cytoplasm
early endosome membrane
endocytic vesicle
endoplasmic reticulum membrane
endosome
endosome membrane
extracellular space
focal adhesion
Golgi membrane
integral component of membrane
membrane
membrane raft
multivesicular body, internal vesicle lumen
nuclear membrane
nucleus
perinuclear region of cytoplasm
plasma membrane
receptor complex
Shc-EGFR complex
actin filament binding
ATP binding
chromatin binding
double-stranded DNA binding
enzyme binding
epidermal growth factor-activated receptor activity
identical protein binding
MAP kinase kinase kinase activity
protein heterodimerization activity
protein phosphatase binding
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
transmembrane signaling receptor activity
ubiquitin protein ligase binding
activation of MAPKK activity
activation of phospholipase A2 activity by calcium-mediated signaling
activation of phospholipase C activity
axon guidance
cell proliferation
cell surface receptor signaling pathway
cellular response to amino acid stimulus
cellular response to epidermal growth factor stimulus
cellular response to estradiol stimulus
cerebral cortex cell migration
digestive tract morphogenesis
embryonic placenta development
epidermal growth factor receptor signaling pathway
eyelid development in camera-type eye
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
hair follicle development
innate immune response
insulin receptor signaling pathway
learning or memory
MAPK cascade
morphogenesis of an epithelial fold
negative regulation of apoptotic process
negative regulation of epidermal growth factor receptor signaling pathway
negative regulation of protein catabolic process
neurotrophin TRK receptor signaling pathway
ossification
peptidyl-tyrosine phosphorylation
phosphatidylinositol-mediated signaling
positive regulation of catenin import into nucleus
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
positive regulation of DNA repair
positive regulation of DNA replication
positive regulation of epithelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of fibroblast proliferation
positive regulation of MAP kinase activity
positive regulation of nitric oxide biosynthetic process
positive regulation of phosphorylation
positive regulation of protein kinase B signaling
positive regulation of protein phosphorylation
positive regulation of transcription from RNA polymerase II promoter
protein autophosphorylation
protein insertion into membrane
Ras protein signal transduction
regulation of nitric-oxide synthase activity
regulation of peptidyl-tyrosine phosphorylation
response to stress
response to UV-A
salivary gland morphogenesis
signal transduction
single organismal cell-cell adhesion
small GTPase mediated signal transduction
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:
activation of MAPKK activity
activation of phospholipase A2 activity by calcium-mediated signaling
activation of phospholipase C activity
axon guidance
cell proliferation
cell surface receptor signaling pathway
cellular response to amino acid stimulus
cellular response to epidermal growth factor stimulus
cellular response to estradiol stimulus
cerebral cortex cell migration
digestive tract morphogenesis
embryonic placenta development
epidermal growth factor receptor signaling pathway
eyelid development in camera-type eye
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
hair follicle development
innate immune response
insulin receptor signaling pathway
learning or memory
MAPK cascade
morphogenesis of an epithelial fold
negative regulation of apoptotic process
negative regulation of epidermal growth factor receptor signaling pathway
negative regulation of protein catabolic process
neurotrophin TRK receptor signaling pathway
ossification
peptidyl-tyrosine phosphorylation
phosphatidylinositol-mediated signaling
positive regulation of catenin import into nucleus
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
positive regulation of DNA repair
positive regulation of DNA replication
positive regulation of epithelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of fibroblast proliferation
positive regulation of MAP kinase activity
positive regulation of nitric oxide biosynthetic process
positive regulation of phosphorylation
positive regulation of protein kinase B signaling
positive regulation of protein phosphorylation
positive regulation of transcription from RNA polymerase II promoter
protein autophosphorylation
protein insertion into membrane
Ras protein signal transduction
regulation of nitric-oxide synthase activity
regulation of peptidyl-tyrosine phosphorylation
response to stress
response to UV-A
salivary gland morphogenesis
signal transduction
single organismal cell-cell adhesion
small GTPase mediated signal transduction
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:
actin filament binding
ATP binding
chromatin binding
double-stranded DNA binding
enzyme binding
epidermal growth factor-activated receptor activity
identical protein binding
MAP kinase kinase kinase activity
protein heterodimerization activity
protein phosphatase binding
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
transmembrane signaling receptor activity
ubiquitin protein ligase binding
Gene Ontology Cellular Component:
basolateral plasma membrane
cell surface
cytoplasm
early endosome membrane
endocytic vesicle
endoplasmic reticulum membrane
endosome
endosome membrane
extracellular space
focal adhesion
Golgi membrane
integral component of membrane
membrane
membrane raft
multivesicular body, internal vesicle lumen
nuclear membrane
nucleus
perinuclear region of cytoplasm
plasma membrane
receptor complex
Shc-EGFR complex
Keywords:
3D-structure
ATP-binding
Alternative splicing
Cell membrane
Complete proteome
Developmental protein
Direct protein sequencing
Disease mutation
Disulfide bond
Endoplasmic reticulum
Endosome
Glycoprotein
Golgi apparatus
Isopeptide bond
Kinase
Membrane
Methylation
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tumor suppressor
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
Itself; Q53FC7; Q96BE0; P00519; P42684; Q09666; Q02952; Q92625; Q96CW1; O00213; Q92870; O95704; Q9UKG1; O14965; P30530; Q14457; P51451; P62158; P62161; P49069; Q03135; P22681; P22682; Q16543; P12830; Q9NSE2; Q7Z7G1; P46108; P46108-1; P46109; P35221; O60716; Q14247; Q99418; Q6PKX4; P01133; Q12929; P04626; P21860; Q15303; P07992; Q9UJM3; P03372; P03372-4; Q96A65; P09769; Q14318; Q13480; P60520; P04406; O75791; P62993; P08631; Q9UBN7; Q8WUI4; P07900; P08238; Q6PK50; P08107; P11142; P38646; P04792; P17936; P46940; O14654; Q86VI4; O43561; Q13094; Q38SD2; P07948; P07948-1; Q9UQF2; Q13387; Q9Y2H9; P08581; P15941; P16333; P04150; P16234; O00750; P27986; O00459; Q92569; P19174; P16885; P17252; P97313; Q05397; P18031; P20417; Q05209; Q9Y2R2; Q9UJ41; Q70E73; P20936; Q13671; Q01973; Q92622; Q80U62; P31947; Q9NRF2; Q9UQQ2; Q9BRG2; P29353; P29353-7; P98077; Q6S5L8; Q13239; P13866; P12931; P42224; P40763; P42229; P31948; Q9UNE7; P43405; P01135; Q9Y490; O60603; Q68CZ2; O75674; Q12933; Q8K424; Q71U36; P10599; P09936; Q9P0L0; P07947; P27348; P63104; P43403

Publication

PubMed ID:
6328312 7654368 8918811 9103388 11161793 6326261 6330563 6093780 3329716 1988448 2991899 6324343 3138233 15340161 2985580 16543144 9556602 6325948 3039909 2790960 2543678 7679104 8650580 9852145 10523301 8144591 7657591 8962717 9419975 9488479 10228163 10026169 10731668 11602604 12731890 12873986 15282549 10805725 11116146 11483589 15590694 15611079 16083266 16140940 17081983 17115032 17671655 17182860 18602463 19172738 18220336 18691976 18669648 19413330 19836242 19509291 19159218 19369195 19749156 20674546 20551055 20068231 21269460 21487020 21258366 21518868 22298428 22179831 23418353 24275569 25311788 23912460 12297050 12620237 15374980 15837620 15840573 17349580 18046415 18227510 19563760 19560417 20471394 20837704 22888118 15623594 15118125 16533793 16205628 16672372 17344846 24691054