Biomarker: EGFR

Histology type: endometrial carcinoma

Country: USA

Region: Oklahoma

Followed up time :

Subgroup 1 name : positive

Subgroup 1 number: 34

Subgroup 2 name: negative

Subgroup 2 number: 32

Conclusion: EGFR strongly correlates with tumor metastasis and patient survival in endometrial cancer. Altered expression of this oncoprotein may serve as a guide to prognosis and treatment in these patients.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : overexpression

Expression elevation: Expression of EGFR and HER-2/neu was in-dicated by their specific cell membrane positivity. In fivecases, EGFR immunoreactivity was given by cytoplasmicstaining.

Statictics: Mean (SD);Range

Cohort age: 62.3±12.5;29-87

Funtion Uniprot: 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).By Similarity22 Publications 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.1 Publication

UniProt ID: P00533

UniProt Link: https://www.uniprot.org/uniprotkb/P00533/entry

Biological function from UniProt: #Host-virus interaction

Molecular function from UniProt:

Tissue specificity from UniProt: Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers.

Subcellular UniProt: #Cell membrane #Endoplasmic reticulum #Endosome #Golgi apparatus #Membrane

Alternative name from UniProt:

Catalytic activity: ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]

Activity regulation: Endocytosis and inhibition of the activated EGFR by phosphatases like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling. Up-regulated by NEU3-mediated desialylation of N-linked glycan at Asn-528.

Recommended name: Epidermal growth factor receptor

Gene name from HGNC: EGFR (ERBB, ERBB1)

HPA class: Cancer-related genes Disease related genes Enzymes FDA approved drug targets Human disease related genes Metabolic proteins Plasma proteins RAS pathway related proteins

AlphaFold DB: P00533

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P00533

HPA link: https://www.proteinatlas.org/ENSG00000146648-EGFR

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Membranous and cytoplasmic expression in several tissues, most abundant in placenta.

Single cell type specificity Cell type enhanced (Syncytiotrophoblasts, Cytotrophoblasts, Skeletal myocytes)

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Plasma membrane, Cell Junctions

Cancer prognostic summary HPA Prognostic marker in urothelial cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000146648-EGFR/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000146648-EGFR/pathology/endometrial+cancer

Phenotype ID: 211980$ 616069

Disease: Lung cancer (LNCR)$ Inflammatory skin and bowel disease, neonatal, 2 (NISBD2)

Note1: The gene represented in this entry is involved in disease pathogenesis$ The disease is caused by variants affecting the gene represented in this entry

OMIM: 131550

OMIM link1: https://www.omim.org/entry/211980$https://www.omim.org/entry/616069

OMIM link2: https://www.omim.org/entry/131550

HGNC ID: HGNC:3236

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3236