DegronMD - P00533(EGFR)

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, PubMed:17909029). 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). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (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. {ECO:0000269|PubMed:21516087}. View more >>

GO - Biological processes (BP): activation of phospholipase A2 activity by calcium-mediated signaling [GO:0043006]; activation of phospholipase C activity [GO:0007202]; cell-cell adhesion [GO:0098609]; cell differentiation [GO:0030154]; cell morphogenesis [GO:0000902]; cell surface receptor signaling pathway [GO:0007166]; cellular response to amino acid stimulus [GO:0071230]; cellular response to cadmium ion [GO:0071276]; cellular response to epidermal growth factor stimulus [GO:0071364]; cellular response to estradiol stimulus [GO:0071392]; cellular response to reactive oxygen species [GO:0034614]; cerebral cortex cell migration [GO:0021795]; digestive tract morphogenesis [GO:0048546]; embryonic placenta development [GO:0001892]; epidermal growth factor receptor signaling pathway [GO:0007173]; eyelid development in camera-type eye [GO:0061029]; hair follicle development [GO:0001942]; learning or memory [GO:0007611]; morphogenesis of an epithelial fold [GO:0060571]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cardiocyte differentiation [GO:1905208]; negative regulation of epidermal growth factor receptor signaling pathway [GO:0042059]; negative regulation of protein catabolic process [GO:0042177]; ossification [GO:0001503]; peptidyl-tyrosine autophosphorylation [GO:0038083]; peptidyl-tyrosine phosphorylation [GO:0018108]; positive regulation of canonical Wnt signaling pathway [GO:0090263]; positive regulation of cell growth [GO:0030307]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0045737]; positive regulation of DNA repair [GO:0045739]; positive regulation of DNA replication [GO:0045740]; positive regulation of epithelial cell proliferation [GO:0050679]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of G1/S transition of mitotic cell cycle [GO:1900087]; positive regulation of kinase activity [GO:0033674]; positive regulation of MAP kinase activity [GO:0043406]; positive regulation of NIK/NF-kappaB signaling [GO:1901224]; positive regulation of nitric oxide mediated signal transduction [GO:0010750]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of phosphorylation [GO:0042327]; positive regulation of production of miRNAs involved in gene silencing by miRNA [GO:1903800]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of protein kinase C activity [GO:1900020]; positive regulation of protein localization to plasma membrane [GO:1903078]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein autophosphorylation [GO:0046777]; protein insertion into membrane [GO:0051205]; regulation of ERK1 and ERK2 cascade [GO:0070372]; regulation of JNK cascade [GO:0046328]; regulation of nitric-oxide synthase activity [GO:0050999]; regulation of peptidyl-tyrosine phosphorylation [GO:0050730]; regulation of phosphatidylinositol 3-kinase signaling [GO:0014066]; response to UV-A [GO:0070141]; salivary gland morphogenesis [GO:0007435]; signal transduction [GO:0007165]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R1068Q	TCGA-06-5416	GBM	TCGA	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation altering degron motif	0.6218
p.D1084N	TCGA-A5-A0G1	UCEC	TCGA	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation altering degron motif	0.5821
p.I706L	TCGA-A5-A0G2	UCEC	TCGA	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.0833
p.V1097I	TCGA-AD-6964	COAD	TCGA	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.1944
p.V1097I	TCGA-C5-A2M2	CESC	TCGA	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.1944
p.V1097I	DO48984	CESC	ICGC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.1944
p.V1097I	DO8360	COAD	ICGC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.1944
p.R681M	TCGA-AP-A1DK	UCEC	TCGA	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.0556
p.Q684H	TCGA-AX-A1CE	UCEC	TCGA	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1389
p.P694S	TCGA-B5-A0JZ	UCEC	TCGA	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.6752
p.S1096F	TCGA-D5-6928	COAD	TCGA	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation blocking phosphorylation signal	0.6667
p.S1096F	DO7776	COAD	ICGC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation blocking phosphorylation signal	0.6667
p.N1094S	TCGA-DI-A1BU	UCEC	TCGA	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.2778
p.N1094S	DO42023	UCEC	ICGC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.2778
p.E1079K	TCGA-DK-A3WW	BLCA	TCGA	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.2222
p.E1079K	TCGA-DK-A3WW	BLCA	TCGA	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation rewiring degron network	0.1667
p.P699L	TCGA-FR-A726	SKCM	TCGA	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.2778
p.S694C	DO49964	CESC	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7541
p.D1087H	DO233726	GACA	ICGC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation altering degron motif	0.7688
p.I699F	DO44440	HNSC	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.2778
p.V697F	DO229018	LICA	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7068
p.I699V	DO52258	LIHC	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.2778
p.P696R	DO220891	MELA	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7512
p.K692E	DO222775	MELA	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7022
p.K692E	DO47665	SKCM	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7022
p.E1083D	DO222875	MELA	ICGC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation altering degron motif	0.6758
p.L1075I	DO232224	PBCA	ICGC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.1111
p.L1075I	DO232224	PBCA	ICGC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation rewiring degron network	0.2778
p.P696L	DO220239	SARC	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7582
p.G682C	DO47407	SKCM	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.0833
p.W683R	DO219466	SKCM	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1111
p.V697I	DO40900	UCEC	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7076
p.V697I	ACH-000368	Brain Cancer	CCLE	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7076
p.V697M	DO42033	UCEC	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7208
p.A698T	DO41235	UCEC	ICGC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.3056
p.S703F	SIDM01116	Non-Small Cell Lung Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM00855	Other Sarcomas	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM00210	Ovarian Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM01112	Osteosarcoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM00529	Breast Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM00052	Esophageal Squamous Cell Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM00114	Non-Small Cell Lung Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM01147	Gastric Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM01133	Other Solid Cancers	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM00721	Small Cell Lung Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM00720	Mesothelioma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM00628	Breast Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM01318	Hepatocellular Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM01664	Prostate Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM01677	Non-Small Cell Lung Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S703F	SIDM01525	Acute Myeloid Leukemia	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.S1056F	SIDM00042	Pancreatic Carcinoma	GDSC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation rewiring degron network	0.1389
p.S1056F	PL4	pancreas	COSMIC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation rewiring degron network	0.1389
p.Q701R	SIDM01078	Small Cell Lung Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.2222
p.Q701R	SHP-77	lung	COSMIC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.2222
p.T1085N	SIDM00329	Hodgkin's Lymphoma	GDSC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation altering degron motif	0.8166
p.T1085N	L-540	haematopoietic and lymphoid tissue	COSMIC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation altering degron motif	0.8166
p.A702D	SIDM01026	Esophageal Squamous Cell Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1944
p.A702D	KYSE-510	oesophagus	COSMIC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1944
p.P1071L	SIDM00683	Prostate Carcinoma	GDSC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation altering degron motif	0.7582
p.P1071L	LNCaP-Clone-FGC	prostate	COSMIC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation altering degron motif	0.7582
p.Y1069C	SIDM00487	Colorectal Carcinoma	GDSC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation altering degron motif	0.8198
p.Y1069C	CCK-81	large intestine	COSMIC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation altering degron motif	0.8198
p.A1076T	SIDM00429	B-Lymphoblastic Leukemia	GDSC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.1389
p.A1076T	SIDM00429	B-Lymphoblastic Leukemia	GDSC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation rewiring degron network	0.25
p.A1076T	NALM-6	haematopoietic and lymphoid tissue	COSMIC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.1389
p.A1076T	NALM-6	haematopoietic and lymphoid tissue	COSMIC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation rewiring degron network	0.25
p.A1086V	SIDM00429	B-Lymphoblastic Leukemia	GDSC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation altering degron motif	0.6936
p.A1086V	NALM-6	haematopoietic and lymphoid tissue	COSMIC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation altering degron motif	0.6936
p.S1060A	SIDM01066	Melanoma	GDSC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation rewiring degron network	0.25
p.G682V	SIDM00867	Glioblastoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.0833
p.G682V	DBTRG-05MG	central nervous system	COSMIC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.0833
p.E697K	SIDM01588	Endometrial Carcinoma	GDSC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7022
p.T706I	ACH-000817	Myeloma	CCLE	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.0833
p.T706I	RPMI-8226	haematopoietic and lymphoid tissue	COSMIC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.0833
p.R703K	ACH-001566	Skin Cancer	CCLE	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1667
p.V693D	SU-DHL-6	haematopoietic and lymphoid tissue	COSMIC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation altering degron motif	0.7785
p.S1059P	SF295	central nervous system	COSMIC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation rewiring degron network	0.2222
p.E701K	HCC-827	lung	COSMIC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.2222
p.A705E	HCC-827	lung	COSMIC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.1111
p.A1073T	FTC-133	thyroid	COSMIC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation altering degron motif	0.7139
p.A1073T	CCRF-CEM	haematopoietic and lymphoid tissue	COSMIC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation altering degron motif	0.7139
p.D1082N	NCI-H1568	lung	COSMIC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation rewiring degron network	0.3056
p.D1082N	NCI-H1568	lung	COSMIC	DSFLQRYSSDP	CBL_PTK	1063:1073	Mutation rewiring degron network	0.0833
p.E701A	HCC-827	lung	COSMIC	PLTPSGE	DEG_SCF_FBW7_2	691:697	Mutation rewiring degron network	0.2222
p.S1085G	NCI-H2172	lung	COSMIC	DDTFLPVPEY	DEG_COP1_1	1083:1092	Mutation altering degron motif	0.6993

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

EGFR

UniProt ID: P00533

Entrez ID: 1956

Protein name: Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for EGFR in