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FLASH GENE
Symbol EGFR contributors: mct/pgu - updated : 05-11-2019
HGNC name epidermal growth factor receptor
HGNC id 3236
DNA
TYPE functioning gene
STRUCTURE 188.31 kb     28 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked Y status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
28 - 5616 134.3 1210 - 2001 11161793
20 splicing 2239 69.2 628 - 2001 11161793
using a different 3' terminal exon compared to variant 1
10 splicing 1595 44.6 405 . secreted . ovarian cancers 2001 11161793
using a different 3' terminal exon compared to variant 1
20 splicing 2865 77.3 705 . ubiquitous . placenta liver, fetal tissues, brain, kidney, lung 2001 11161793
using a different 3' terminal exon compared to variant 1
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   highly Homo sapiens
 mouthtongue  highly
Reproductivefemale systemplacenta  highly
 female systembreastmammary gland highly
 male systemmale genital tractepididymis   Homo sapiens
Urinarybladder   highly
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticerythroblast
Digestivehepatocyte Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period neonatal
Text rostral subependymal zone of postnatal brain
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an extracellular domain
  • four subdomains (two cysteine rich and two involved in ligand binding)
  • a single transmembrane domain with extensive homology to the epidermal growth factor receptor
  • a cytoplasmic catalytic domain
  • specific N-glycan in domain III playing an essential role in regulating receptor dimerization and transforming activity
  • a putative NLS with three clusters of basic amino acids (RRRHIVRKRTLRR (amino acids 645-657)) in the juxtamembrane region
  • conjugated GlycoP
    mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies ortholog to murine Egfr
    homolog to drosophila Egfr
    homolog to zebrafish egfr
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • EGF receptor subfamily
  • CATEGORY receptor membrane tyrosine kinase
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text
  • type I membrane protein, a secreted isoform
  • translocates to the nucleus in liver cells
  • basic FUNCTION
  • receptor tyrosine kinase, class I, critical regulator of hepatocyte proliferation in the initial phases of liver regeneration
  • acting as a receptor for EGF, but also for other members of the EGF family, as TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30 and vaccinia virus growth factor
  • involved in the control of cell growth and differentiation
  • involved in early craniofacial development and palate closure and in keratinocyte differentiation
  • activating phosphatidylinositol and Ras pathways
  • plays a novel role in modulating mitochondrial function via its association with, and modification of COX2
  • mediating the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth
  • involved in the pathogenesis and progression of different carcinoma types
  • EGFR signaling is negatively regulated by CPEB3 in neurons
  • EGFR-mediated apoptosis is initiated by the activated EGFR from the limiting membrane of the endosome
  • EGFR signaling is required for regenerative proliferation in the cochlea
  • DNM1-mediated endocytosis leads to attenuation of EGFR activation and degradation and stimulation of the MAPK response and AKT1 activation are primarily mediated by activated EGFR located in the plasma membrane
  • internalization and degradation of the EGFR are important for the regulation of EGFR signal transduction
  • is required for KRAS-induced pancreatic tumorigenesis
  • primary role of EGFR signaling in the regulation of prostate carcinoma (PCa) invasiveness, but not of PCa growth
  • critically involved in tissue development and homeostasis as well as in the pathogenesis of cancer
  • component in the regulation of local immune responses that establish a link between mast cells and Treg cells
  • its activation contributed to cell cycle arrest at the G2/M phase, a cellular event associated with production of profibrogenetic factors, in the injured kidney
  • ligand-dependent EGFR activation leads to the interaction of EGFR and BECN1, which likely occurs primarily in endosomes
  • EGFR, CALM3 and SMARCD1 play roles in bone and/or fat metabolism
  • SULF1, SULF2 and EGFR are likely involved in the signalling pathway from chondroitin sulphate proteoglycans (CSPGs)that leads to inhibition of neurite outgrowth and may regulate structural plasticity and regeneration in the nervous system
  • recycling regulator ARHGEF6 and the degradation factor CBL closely cooperate in the regulation of EGFR trafficking
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS development
    text neurogenic potential
    PATHWAY
    metabolism
    signaling signal transduction
  • MAPK signaling pathway
  • calcium signaling pathway
  • critical role of the ADAM17-EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier
  • signaling cascade in which EGFR enhances MCM7 phosphorylation and DNA replication through LYN phosphorylation in human cancer cells
  • a component
  • part of a complex with ERBB2 and either PIK3C2A or PIK3C2B
  • part of EGFR/ERK pathways involved in control of differentiation
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • phosphorylating GJB1 actin cytoskeleton rearrangement resulting in membrane ruffling
  • interacting with RIPK1 (RIPK1 influences EGFR at the mRNA level by regulating the EGFR promoter)
  • stimulating ER phosphorylation on tyrosine and promoting the association of a complex between EGFR, AR/ER, and the kinase Src
  • CBL interacts with the autophosphorylated C-terminal tail of the EGF receptor
  • the autophoshorylated form interacts with PIK3C2B, maybe indirectly
  • key negative regulator of NOTCH1 gene expression in primary keratinocytes, intact epidermis and skin squamous cell carcinomas
  • interaction with ligands having differential effects of EGFR ligands on endocytic sorting of the receptor
  • USP18 overexpression elevated EGFR levels in a manner requiring the catalytic cysteine of USP18
  • interacting with MMP9 (initiates cross-talk between CD44 and EGFR, which in turn activates downstream effectors for cell migration)
  • functional interaction between IQGAP1 and EGFR, suggesting that IQGAP1 modulates EGFR activation
  • LGALS3-dependent regulation of MUC1/EGFR functions may represent an interesting mechanism modulating the EGFR-stimulated cell growth of pancreatic cancer cells
  • USP18 is a potent regulator of EGFR protein expression
  • interacting with dynamin and clathrin that are necessary first steps for translocation of EGFR to the nucleus
  • SRC-dependent link between CHKA and EGFR, which contributes to the regulation of cell proliferation and tumorigenesis
  • cooperation between the EGF/EGFR and PTGES leads to a significant tumorigenic gain in epithelial cells
  • APPL1 function as a downstream effector of EGF-initiated signaling
  • FKBP1A forms an endogenous inhibitor of EGFR phosphorylation directly involved in the control of cellular EGFR activity
  • CDCP1 is a key regulator of EGF/EGFR-induced cell migration
  • STYK1 is likely colocalised with EGFR in endosomes to participate in a post-internalisation step of EGFR
  • enhanced the degradation of EGFR through accelerating its internalization in both EGF-independent and EGF-dependent manners
  • GRB2 mediates the interaction of TNK2 with EGFR through binding to the EBD and activates TNK2 by releasing the auto-inhibition
  • crucial role of cytosolic LGALS3 in controlling intracellular trafficking and cell surface expression of EGFR after EGF stimulation
  • EGFR activation also promotes RIN1 interaction with BIN1, a membrane bending protein
  • oncogenic KRAS upregulates endogenous EGFR expression and activation, the latter being dependent on the EGFR ligand sheddase, ADAM17
  • inhibition of HDAC6 activity accelerated the trafficking of EGFR from early endosomes to late endosomes along the microtubules
  • EGFR, SFKs, and STAT3 can serve as substrates for the protein tyrosine phosphatase TCPTP (PTPN2)
  • role of ADAM17 during embryonic eyelid closure is to transactivate EGFR signaling
  • cross-talk between DSG3 and EGFR, and this cross-talk is regulated by MAPK
  • EGFR suppression of BECN1 may contribute to tumor progression in lung cancer
  • in cancer, simultaneous upregulation of EGFR and secretion of IL6 can cooperate to desensitize the cancer cells to the actions of negative regulators, especially SOCS3
  • BTC binds and activates EGFR and ERBB4 homodimers
  • RASGRP1 creates a negative feedback loop that limits proliferative EGFR-SOS1-RAS signals in colorectal carcinoma cells
  • in ovarian cancer DSC3 and EGFR regulate each other and the activation of the AKT1 pathway, and AKT1 mediates FSH-dependent DSC3 expression
  • TMPRSS11E cleaved EGFR and downregulated the EGFR/AKT pathway to favor apoptosis
  • role of EGFR in modulating cellular iron homeostasis through redistribution of TFRC, which is essential for cancer development and progression
  • CHRM3-induced activation of MAPK14 might contribute to the maintenance of epithelial barrier function through down-regulation of TNF signalling and activation of EGFR
  • SEMA3C drives activation of multiple RTKs including EGFR, ERBB2, and MET in a cognate ligand-independent manner via PLXNB1
  • RNF144A promotes EGFR ubiquitination, maintains EGFR protein, and prolongs EGF/EGFR signaling during EGF stimulation
  • MITF effectively suppresses EGFR and TGFA expression and therefore serves as link between NFE2L2 and EGFR
  • cell & other
    REGULATION
    activated by the formation of an asymmetric dimer in which the C-terminal lobe of one kinase domain plays a role analogous to that of cyclin in activated CDK/cyclin complexes
    by cholesterol depletion of plasma membranes
    inhibited by RIPK1
    GM3 (regulated by its lipid environment and in this context is specifically inhibited by interaction with the ganglioside GM3)
    repressed by ZGPAT recruiting NuRD complex to the promoter
    tubulin acetylation that negatively regulates EGFR levels
    Other phosphorylated by activated MAPK3/MAPK1 couple with the participation of IQGAP1
    VAV2 delays its internalization and degradation and enhances its phosphorylation
    regulation of EGFR vesicular trafficking and degradation by the microtubule deacetylase HDAC6
    regulated by N-glycosylation that controls ErbB signaling by various mechanisms
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in prostate carcinoma, brain astrocytomas and gliomas (tandemly duplicated
    tumoral   deletion    
    in brain glioblastoma
    tumoral somatic mutation      
    in malignant oral keratinocytes and in non-small cell lung cancer of non-smokers
    tumoral   amplification    
    short alleles of polymorphic CA repeat located at a 5-regulatory sequence in the intron 1 associated with increased expression in osteosarcoma
    tumoral   amplification    
    frequent alterations in primary melanomas and associated with bad prognosis
    tumoral     --over  
    correlated with poor prognosis in Glioblastoma multiforme patients
    Susceptibility to non-small cell lung cancer
    Variant & Polymorphism other germline mutation T790M in non-small cell lung cancer, mutation drug resistance, stimulating DNA synthesis and cytoskeletal rearrangement in breast cancer (MCF-7) and prostate cancer (LNCaP) cells
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    important target of cancer drug design (inhibition of EGFR signaling in cancer cells induces NOTCH1 gene expression through TP53)
    cancerlung 
    lung adenocarcinomas with activating mutations in EGFR often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient
    cancerhead and neck 
    dual blockade of MET and EGFR may be a promising clinical therapeutic strategy for treating HNSCC
    dermatologyskin 
    is a potential therapeutic target for pemphigus
    miscelleaneousurinary 
    targeting HDAC6 to downregulate EGFR activity may provide a potential therapeutic approach to treat polycystic kidney disease
    cancerreproductiveprostate
    blockade of EGFR signaling could be more effective in preventing and retarding PCa progression toward metastasis
    miscelleaneousurinarychronic kidney disease
    most promising targets for future therapeutic development in Polycystic kidney disease (PKD)are those that target upstream signaling events at cell membranes, such as the vasopressin-2 receptor (AVPR2), EGFR/ERBB2
    ANIMAL & CELL MODELS