Uniprot ID: P00533	Protein name : Epidermal growth factor receptor	Gene : EGFR ERBB ERBB1 HER1
Protein Families : "Protein kinase superfamily, Tyr protein kinase family, EGF receptor subfamily"	Squence Length : 1210

Sequence	>P00533 1211 MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTEDSIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLNTVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRVAPQSSEFIGA
Repeat regions	REPEAT 75 300 Approximate REPEAT 390 600 Approximate
Sequence region of repeats	75- 300 SFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVT 390- 600 LDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGE
Domains	DOMAIN 712 979 Protein kinase
Function	"Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:2790960, PubMed:10805725, PubMed:27153536). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975, PubMed:15611079, PubMed:12297049, PubMed:27153536, PubMed:20837704). 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 (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). 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 (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Plays a role in enhancing learning and memory performance (By similarity).; Isoform 2 may act as an antagonist of EGF action.; (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins"
Active Site	ACT_SITE 837 837 Proton acceptor
Binding Site	BINDING 745 745 ATP. BINDING 855 855 ATP
Nucleotide Binding	NP_BIND 718 726 ATP. NP_BIND 790 791 ATP
Mutation	"275 275 Y->A: Strongly reduced autophosphorylation and activation of downstream kinases when associated with A-309 287 287 F->A: Strongly reduced autophosphorylation and activation of downstream kinases when associated with A-309 309 309 R->S: Strongly reduced autophosphorylation and activation of downstream kinases when associated with A-275 when associated with A-287 429 429 R->E: Abolishes autophosphorylation and activation of downstream kinases 587 590 DGPH->AGPA: Decreases intramolecular interactions and facilitates EGF binding 609 609 K->A: Decreases intramolecular interactions and facilitates EGF binding 688 688 L->A: Strongly reduced phosphorylation 689 689 V->A: Reduced autophosphorylation 689 689 V->M: Constitutively activated kinase 690 690 E->A: Reduced phosphorylation 692 692 L->A,P: Strongly reduced phosphorylation 693 693 T->A: Increased phosphorylation 693 693 T->D: Strongly reduced phosphorylation 694 694 P->A: Strongly reduced phosphorylation 699 699 P->A: Reduced phosphorylation 700 700 N->A: Abolishes phosphorylation 704 704 L->A: Abolishes phosphorylation 705 705 R->A: Abolishes phosphorylation 706 706 I->A: Abolishes phosphorylation 745 745 K->A,M: Abolishes kinase activity 974 974 D->A: Strongly reduced phosphorylation 977 977 R->A: Reduced phosphorylation 1005 1006 ED->RK: Constitutively activated kinase 1016 1016 Y->F: 50% decrease in interaction with PIK3C2B when associated with F-1197 when associated with F-1197 and F-1092 1048 1210 Missing: Abolishes palmitoylation 1049 1049 C->A: Decreased palmitoylation 1067 1067 Q->G: No effect on interaction with CBLC 1068 1068 R->G: Strongly decreases interaction with CBLC 1069 1069 Y->F: Abolishes interaction with CBLC 1092 1092 Y->F: No change in interaction with PIK3C2B when associated with F-1197 and F-1016 1110 1110 Y->F: No change in interaction with PIK3C2B 1146 1146 C->A: Decreased palmitoylation 1172 1172 Y->F: No change in interaction with PIK3C2B 1197 1197 Y->F: No change in interaction with PIK3C2B when associated with F-1016 when associated with F-1092 and F-1016"
Disease	"DISEASE: 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 Note=The gene represented in this entry is involved in disease pathogenesis ; DISEASE: Inflammatory skin and bowel disease, neonatal, 2 (NISBD2) [MIM:616069]: 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 Note=The disease is caused by mutations affecting the gene represented in this entry"

P00533 Proteins with OtherRepeats Repeats