LipidDB ID

LipidDB-9606-00398

Entry Name

UniProt Accession

P00533; O00688; O00732; P06268; Q14225; Q68GS5; Q92795; Q9BZS2; Q9GZX1; Q9H2C9; Q9H3C9; Q9UMD7; Q9UMD8; Q9UMG5;

Theoretical PI

6.26

Molecular Weight

134277.4

Genbank Protein ID

CAA25240.1; AAB53063.1; AAC50802.1; AAC50804.1; AAC50796.1; AAC50797.1; AAC50798.1; AAC50799.1; AAC50800.1; AAC50801.1; AAG35786.1; AAG35787.1; AAG35788.1; AAG35789.1; AAG35790.1; AAT97979.1; AAS83109.1; AAK01080.1; AAG43240.1; AAG43243.1; AAG43243.1; CAA29668.1; CAA25282.1; AAA63171.1; AAA52370.1;

Genbank Nucleotide ID

X00588; U95089; U48722; U48723; U48724; U48725; U48726; U48727; U48728; U48729; AF288738; AF288738; AF288738; AF288738; AF288738; AY698024; AY588246; AF277897; AF125253; AF125539; AF125538; X06370; X00663; M38425; M11234;

Protein Name

Epidermal growth factor receptor

Protein Synonyms/Alias

2.7.10.1; Proto-oncogene c-ErbB-1; Receptor tyrosine-protein kinase erbB-1;

Gene Name

EGFR

Gene Synonyms/Alias

ERBB; ERBB1; HER1;

Created Date

21-JUL-1986

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Bollu LR, Ren J, Blessing AM, Katreddy RR, Gao G, Xu L, Wang J, Su F, WeihuaZ. Involvement of de novo synthesized palmitate and mitochondrial EGFR in EGFinduced mitochondrial fusion of cancer cells. Cell Cycle. 2014 Jun 24;13(15).[Epub ahead of print][PMID:24959831]

Functional Description

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.

Sequence Annotation

Topological domain: 25 645 Extracellular.
Transmembrane: 646 668 Helical.
Topological domain: 669 1210 Cytoplasmic.
Domain: 712 979 Protein kinase.
Nucleotide-binding: 718 726 ATP.
Nucleotide-binding: 790 791 ATP.
Region: 688 704 Important for dimerization,phosphorylation and activation.
Active site: 837 837 Proton acceptor.
Binding site: 745 745 ATP.
Binding site: 855 855 ATP.
Functional site: 1016 1016 Important for interaction with PIK3C2B.
Modified residue: 229 229 Phosphoserine.
Modified residue: 678 678 Phosphothreonine; by PKC and PKD/PRKD1.
Modified residue: 693 693 Phosphothreonine; by PKD/PRKD1.
Modified residue: 695 695 Phosphoserine.
Modified residue: 991 991 Phosphoserine.
Modified residue: 995 995 Phosphoserine.
Modified residue: 998 998 Phosphotyrosine; by autocatalysis.
Modified residue: 1016 1016 Phosphotyrosine; by autocatalysis.
Modified residue: 1026 1026 Phosphoserine.
Modified residue: 1039 1039 Phosphoserine.
Modified residue: 1041 1041 Phosphothreonine.
Modified residue: 1042 1042 Phosphoserine.
Modified residue: 1064 1064 Phosphoserine.
Modified residue: 1069 1069 Phosphotyrosine.
Modified residue: 1070 1070 Phosphoserine.
Modified residue: 1071 1071 Phosphoserine.
Modified residue: 1081 1081 Phosphoserine.
Modified residue: 1092 1092 Phosphotyrosine; by autocatalysis.
Modified residue: 1110 1110 Phosphotyrosine; by autocatalysis.
Modified residue: 1166 1166 Phosphoserine.
Modified residue: 1172 1172 Phosphotyrosine; by autocatalysis.
Modified residue: 1197 1197 Phosphotyrosine; by autocatalysis.
Modified residue: 1199 1199 Omega-N-methylarginine.

Protein Length

1210 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0016324; C:apical plasma membrane; IEA:Ensembl
GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL
GO:0009986; C:cell surface; IEA:Ensembl
GO:0005737; C:cytoplasm; IDA:UniProtKB
GO:0030139; C:endocytic vesicle; IEA:Ensembl
GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW
GO:0005768; C:endosome; IDA:UniProtKB
GO:0010008; C:endosome membrane; IDA:UniProtKB
GO:0005615; C:extracellular space; NAS:UniProtKB
GO:0005925; C:focal adhesion; IDA:UniProtKB
GO:0005794; C:Golgi apparatus; IEA:UniProtKB-KW
GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW
GO:0016020; C:membrane; IDA:UniProtKB
GO:0045121; C:membrane raft; IDA:UniProtKB
GO:0005634; C:nucleus; IDA:UniProtKB
GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl
GO:0005886; C:plasma membrane; IDA:HGNC
GO:0043235; C:receptor complex; IDA:MGI
GO:0070435; C:Shc-EGFR complex; ISS:BHF-UCL
GO:0051015; F:actin filament binding; IDA:UniProtKB
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0003682; F:chromatin binding; IDA:UniProtKB
GO:0003690; F:double-stranded DNA binding; NAS:UniProtKB
GO:0019899; F:enzyme binding; IPI:UniProtKB
GO:0005006; F:epidermal growth factor-activated receptor activity; IDA:UniProtKB
GO:0042802; F:identical protein binding; IPI:IntAct
GO:0004709; F:MAP kinase kinase kinase activity; NAS:UniProtKB
GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB
GO:0019903; F:protein phosphatase binding; IPI:UniProtKB
GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB
GO:0004716; F:receptor signaling protein tyrosine kinase activity; IEA:InterPro
GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; TAS:Reactome
GO:0004888; F:transmembrane signaling receptor activity; IDA:MGI
GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB
GO:0043006; P:activation of phospholipase A2 activity by calcium-mediated signaling; TAS:UniProtKB
GO:0007202; P:activation of phospholipase C activity; TAS:UniProtKB
GO:0019694; P:alkanesulfonate metabolic process; IEA:Ensembl
GO:0048143; P:astrocyte activation; IEA:Ensembl
GO:0007411; P:axon guidance; TAS:Reactome
GO:0008283; P:cell proliferation; IDA:UniProtKB
GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI
GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl
GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl
GO:0035690; P:cellular response to drug; IEA:Ensembl
GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB
GO:0071392; P:cellular response to estradiol stimulus; IDA:UniProtKB
GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl
GO:0021795; P:cerebral cortex cell migration; IEA:Ensembl
GO:0007623; P:circadian rhythm; IEA:Ensembl
GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl
GO:0016101; P:diterpenoid metabolic process; IEA:Ensembl
GO:0001892; P:embryonic placenta development; IEA:Ensembl
GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB
GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome
GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome
GO:0001942; P:hair follicle development; IEA:Ensembl
GO:0042743; P:hydrogen peroxide metabolic process; IEA:Ensembl
GO:0045087; P:innate immune response; TAS:Reactome
GO:0007611; P:learning or memory; ISS:UniProtKB
GO:0001889; P:liver development; IEA:Ensembl
GO:0030324; P:lung development; IEA:Ensembl
GO:0010960; P:magnesium ion homeostasis; IEA:Ensembl
GO:0000165; P:MAPK cascade; NAS:GOC
GO:0060571; P:morphogenesis of an epithelial fold; IEA:Ensembl
GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB
GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome
GO:0045930; P:negative regulation of mitotic cell cycle; IEA:Ensembl
GO:0042177; P:negative regulation of protein catabolic process; IDA:UniProtKB
GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome
GO:0001503; P:ossification; NAS:UniProtKB
GO:0042698; P:ovulation cycle; IEA:Ensembl
GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:GOC
GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome
GO:0005976; P:polysaccharide metabolic process; IEA:Ensembl
GO:0035413; P:positive regulation of catenin import into nucleus; IMP:BHF-UCL
GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB
GO:0008284; P:positive regulation of cell proliferation; IDA:MGI
GO:0031659; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IDA:BHF-UCL
GO:0045739; P:positive regulation of DNA repair; IDA:UniProtKB
GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB
GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:UniProtKB
GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB
GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl
GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl
GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB
GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:UniProtKB
GO:0042327; P:positive regulation of phosphorylation; IDA:UniProtKB
GO:0051897; P:positive regulation of protein kinase B signaling; IMP:BHF-UCL
GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB
GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl
GO:0032930; P:positive regulation of superoxide anion generation; IEA:Ensembl
GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IEA:Ensembl
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB
GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl
GO:0045909; P:positive regulation of vasodilation; IEA:Ensembl
GO:0046777; P:protein autophosphorylation; IMP:UniProtKB
GO:0051205; P:protein insertion into membrane; TAS:UniProtKB
GO:0050999; P:regulation of nitric-oxide synthase activity; IDA:UniProtKB
GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IMP:UniProtKB
GO:0051592; P:response to calcium ion; IEA:Ensembl
GO:0033590; P:response to cobalamin; IEA:Ensembl
GO:0033594; P:response to hydroxyisoflavone; IEA:Ensembl
GO:0006970; P:response to osmotic stress; IEA:Ensembl
GO:0006979; P:response to oxidative stress; IEA:Ensembl
GO:0006950; P:response to stress; NAS:UniProtKB
GO:0070141; P:response to UV-A; IDA:BHF-UCL
GO:0007435; P:salivary gland morphogenesis; IEA:Ensembl
GO:0007165; P:signal transduction; IDA:UniProtKB
GO:0016337; P:single organismal cell-cell adhesion; IMP:UniProtKB
GO:0043586; P:tongue development; IEA:Ensembl
GO:0006412; P:translation; IEA:Ensembl

Interpro

InterPro; IPR000494; EGF_rcpt_L
InterPro; IPR006211; Furin-like_Cys-rich_dom
InterPro; IPR006212; Furin_repeat
InterPro; IPR009030; Growth_fac_rcpt_N_dom
InterPro; IPR011009; Kinase-like_dom
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom
InterPro; IPR008266; Tyr_kinase_AS
InterPro; IPR020635; Tyr_kinase_cat_dom
InterPro; IPR016245; Tyr_kinase_EGF/ERB/XmrK_rcpt

Pfam

Pfam; PF00757; Furin-like;
Pfam; PF07714; Pkinase_Tyr;
Pfam; PF01030; Recep_L_domain;

SMART

SMART; SM00261; FU;
SMART; SM00219; TyrKc;

PROSITE

PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00109; PROTEIN_KINASE_TYR;

PRINTS

PRINTS; PR00109; TYRKINASE;