InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: EGFR

Summary

InnateDB Protein

IDBP-16935.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

EGFR

Protein Name

epidermal growth factor receptor

Synonyms

ERBB; ERBB1; HER1; mENA; PIG61;

Species

Homo sapiens

Ensembl Protein

ENSP00000275493

InnateDB Gene

IDBG-16933 (EGFR)

Protein Structure

UniProt Annotation

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.

Subcellular Localization

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.

Disease Associations

Lung cancer (LNCR) [MIM:211980]: 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. {ECO:0000269PubMed:15118125, ECO:0000269PubMed:16533793, ECO:0000269PubMed:16672372}. Note=The gene represented in this entry is involved in disease pathogenesis.

Tissue Specificity

Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers. {ECO:0000269PubMed:17671655}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 800 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.

Experimentally validated
Total	800 [view]
Protein-Protein	790 [view]
Protein-DNA	9 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	21 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001948	glycoprotein binding
GO:0003682	chromatin binding
GO:0003690	double-stranded DNA binding
GO:0004672	protein kinase activity
GO:0004709	MAP kinase kinase kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0004716	receptor signaling protein tyrosine kinase activity
GO:0004871	signal transducer activity
GO:0004888	transmembrane signaling receptor activity
GO:0005006	epidermal growth factor-activated receptor activity
GO:0005102	receptor binding
GO:0005178	integrin binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0019903	protein phosphatase binding
GO:0030235	nitric-oxide synthase regulator activity
GO:0042802	identical protein binding
GO:0046982	protein heterodimerization activity
GO:0048408	epidermal growth factor binding
GO:0051015	actin filament binding

Biological Process

GO:0000165	MAPK cascade
GO:0000186	activation of MAPKK activity
GO:0000902	cell morphogenesis
GO:0001503	ossification
GO:0001889	liver development
GO:0001892	embryonic placenta development
GO:0001934	positive regulation of protein phosphorylation
GO:0001942	hair follicle development
GO:0006412	translation
GO:0006468	protein phosphorylation
GO:0006950	response to stress
GO:0006970	response to osmotic stress
GO:0006979	response to oxidative stress
GO:0007165	signal transduction
GO:0007166	cell surface receptor signaling pathway
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007202	activation of phospholipase C activity
GO:0007411	axon guidance
GO:0007435	salivary gland morphogenesis
GO:0007611	learning or memory
GO:0007623	circadian rhythm
GO:0008283	cell proliferation
GO:0008284	positive regulation of cell proliferation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0008544	epidermis development
GO:0010960	magnesium ion homeostasis
GO:0014070	response to organic cyclic compound
GO:0016101	diterpenoid metabolic process
GO:0016337	single organismal cell-cell adhesion
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019694	alkanesulfonate metabolic process
GO:0021795	cerebral cortex cell migration
GO:0023014	signal transduction by phosphorylation
GO:0030324	lung development
GO:0030335	positive regulation of cell migration
GO:0031659	positive regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0032355	response to estradiol
GO:0032930	positive regulation of superoxide anion generation
GO:0033590	response to cobalamin
GO:0033594	response to hydroxyisoflavone
GO:0033993	response to lipid
GO:0035413	positive regulation of catenin import into nucleus
GO:0035556	intracellular signal transduction
GO:0035690	cellular response to drug
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042059	negative regulation of epidermal growth factor receptor signaling pathway
GO:0042127	regulation of cell proliferation
GO:0042177	negative regulation of protein catabolic process
GO:0042327	positive regulation of phosphorylation
GO:0042698	ovulation cycle
GO:0042743	hydrogen peroxide metabolic process
GO:0043006	activation of phospholipase A2 activity by calcium-mediated signaling
GO:0043066	negative regulation of apoptotic process
GO:0043406	positive regulation of MAP kinase activity
GO:0043586	tongue development
GO:0045087	innate immune response (InnateDB)
GO:0045429	positive regulation of nitric oxide biosynthetic process
GO:0045739	positive regulation of DNA repair
GO:0045740	positive regulation of DNA replication
GO:0045907	positive regulation of vasoconstriction
GO:0045909	positive regulation of vasodilation
GO:0045930	negative regulation of mitotic cell cycle
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0048143	astrocyte activation
GO:0048146	positive regulation of fibroblast proliferation
GO:0048546	digestive tract morphogenesis
GO:0048661	positive regulation of smooth muscle cell proliferation
GO:0048812	neuron projection morphogenesis
GO:0050679	positive regulation of epithelial cell proliferation
GO:0050729	positive regulation of inflammatory response
GO:0050730	regulation of peptidyl-tyrosine phosphorylation
GO:0050999	regulation of nitric-oxide synthase activity
GO:0051205	protein insertion into membrane
GO:0051592	response to calcium ion
GO:0051897	positive regulation of protein kinase B signaling
GO:0051968	positive regulation of synaptic transmission, glutamatergic
GO:0060571	morphogenesis of an epithelial fold
GO:0070141	response to UV-A
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0071230	cellular response to amino acid stimulus
GO:0071260	cellular response to mechanical stimulus
GO:0071363	cellular response to growth factor stimulus
GO:0071364	cellular response to epidermal growth factor stimulus
GO:0071392	cellular response to estradiol stimulus
GO:0071549	cellular response to dexamethasone stimulus

Cellular Component

GO:0000139	Golgi membrane
GO:0005615	extracellular space
GO:0005622	intracellular
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005768	endosome
GO:0005789	endoplasmic reticulum membrane
GO:0005886	plasma membrane
GO:0009986	cell surface
GO:0010008	endosome membrane
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016323	basolateral plasma membrane
GO:0016324	apical plasma membrane
GO:0030122	AP-2 adaptor complex
GO:0030139	endocytic vesicle
GO:0031965	nuclear membrane
GO:0043235	receptor complex
GO:0045121	membrane raft
GO:0048471	perinuclear region of cytoplasm
GO:0070435	Shc-EGFR complex

Protein Structure and Domains

PDB ID

InterPro

IPR000494 EGF receptor, L domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR006211 Furin-like cysteine-rich domain
IPR006212 Furin-like repeat
IPR009030 Insulin-like growth factor binding protein, N-terminal
IPR011009 Protein kinase-like domain
IPR016245 Tyrosine protein kinase, EGF/ERB/XmrK receptor
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF01030
PF00069
PF07714
PF00757

PRINTS

PR00109

PIRSF

PIRSF000619

SMART

SM00220
SM00261
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References