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epidermal growth factor receptor; receptor tyrosine-protein kinase ErbB-1 (EGFR, ERBB1, HER1)

Function: - tyrosine kinase receptor - receptor for EGF, & other members of the EGF family including: a) TGF-alpha b) amphiregulin c) betacellulin d) heparin-binding EGF-like growth factor e) GP30 f) vaccinia virus growth factor - role in RAS signal transduction & MAP kinase pathways - role in control of cell growth & differentiation - phosphorylates MUC1 in breast cancer cells & increases the interaction of MUC1 with C-SRC & CTNNB1/beta-catenin - isoform 2/truncated isoform may act as an antagonist - binds RIPK1 - CBL interacts with the autophosphorylated C-terminal tail of the EGF receptor - part of a complex with ERBB2 & either PIK3C2A or PIK3C2B - autophosphorylated form interacts with PIK3C2B, maybe indirectly - interacts with PELP1 - binds MUC1 - phosphorylation of Ser-695 is partial & occurs only if Thr-693 is phosphorylated - monoubiquitinated & polyubiquitinated upon EGF stimulation which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting - polyubiquitin linkage is mainly through Lys-63, but linkage through Lys-48, Lys-11 & Lys-29 also occur - binding of EGF to the receptor leads to dimerization, internalization, induction of tyrosine kinase activity, stimulation of cell DNA synthesis, & cell proliferation Structure: - belongs to the protein kinase superfamily, Tyr protein kinase family, EGF receptor subfamily - contains 1 protein kinase domain Compartment: - cell membrane - isoform 2: secreted Alternative splicing: named isoforms=4 Expression: - ubiquitously expressed Pathology: - defects in EGFR are associated with NSCLC (non-small cell lung carcinoma) - isoform 2 is also expressed in ovarian cancers

Interactions

molecular events

Related

epidermal growth factor (EGF) receptor Ag in tissue epidermal growth factor (EGF) receptor in tissue epidermal growth factor (EGF)/urogastrone erbB proto-oncogene (erb-B1)

General

EGF receptor family protein or erbB proto-oncogene protein glycoprotein PEST protein

Properties

SIZE: entity length = 1210 aa MW = 134 kD COMPARTMENT: cellular membrane STATE: active state MOTIF: signal sequence {1-24} cysteine residue {C31} MODIFICATION: cysteine residue {C58} N-glycosylation site {N56} cysteine residue {C58} MODIFICATION: cysteine residue {C31} Approximate {75-300} MOTIF: N-glycosylation site {N128} cysteine residue {C157} MODIFICATION: cysteine residue {C187} N-glycosylation site {N175} cysteine residue {C187} MODIFICATION: cysteine residue {C157} cysteine residue {C190} MODIFICATION: cysteine residue {C199} cysteine residue {C194} MODIFICATION: cysteine residue {C207} N-glycosylation site {N196} cysteine residue {C199} MODIFICATION: cysteine residue {C190} cysteine residue {C207} MODIFICATION: cysteine residue {C194} cysteine residue {C215} MODIFICATION: cysteine residue {C223} cysteine residue {C219} MODIFICATION: cysteine residue {C231} cysteine residue {C223} MODIFICATION: cysteine residue {C215} cysteine residue {C231} MODIFICATION: cysteine residue {C219} cysteine residue {C232} MODIFICATION: cysteine residue {C240} cysteine residue {C236} MODIFICATION: cysteine residue {C248} cysteine residue {C240} MODIFICATION: cysteine residue {C232} cysteine residue {C248} MODIFICATION: cysteine residue {C236} cysteine residue {C251} MODIFICATION: cysteine residue {C260} cysteine residue {C260} MODIFICATION: cysteine residue {C251} cysteine residue {C264} MODIFICATION: cysteine residue {C291} cysteine residue {C291} MODIFICATION: cysteine residue {C264} cysteine residue {C295} MODIFICATION: cysteine residue {C307} cysteine residue {C307} MODIFICATION: cysteine residue {C295} cysteine residue {C311} MODIFICATION: cysteine residue {C326} cysteine residue {C326} MODIFICATION: cysteine residue {C311} cysteine residue {C329} MODIFICATION: cysteine residue {C333} cysteine residue {C333} MODIFICATION: cysteine residue {C329} cysteine residue {C337} MODIFICATION: cysteine residue {C362} N-glycosylation site {N352} N-glycosylation site {N361} cysteine residue {C362} MODIFICATION: cysteine residue {C337} Approximate {390-600} MOTIF: N-glycosylation site {N413} N-glycosylation site {N444} cysteine residue {C470} MODIFICATION: cysteine residue {C499} cysteine residue {C499} MODIFICATION: cysteine residue {C470} cysteine residue {C506} MODIFICATION: cysteine residue {C515} cysteine residue {C510} MODIFICATION: cysteine residue {C523} cysteine residue {C515} MODIFICATION: cysteine residue {C506} cysteine residue {C523} MODIFICATION: cysteine residue {C510} cysteine residue {C526} MODIFICATION: cysteine residue {C535} N-glycosylation site {N528} cysteine residue {C535} MODIFICATION: cysteine residue {C526} cysteine residue {C539} MODIFICATION: cysteine residue {C555} cysteine residue {C555} MODIFICATION: cysteine residue {C539} cysteine residue {C558} MODIFICATION: cysteine residue {C571} cysteine residue {C562} MODIFICATION: cysteine residue {C579} N-glycosylation site {N568} cysteine residue {C571} MODIFICATION: cysteine residue {C558} cysteine residue {C579} MODIFICATION: cysteine residue {C562} cysteine residue {C582} MODIFICATION: cysteine residue {C591} cysteine residue {C591} MODIFICATION: cysteine residue {C582} cysteine residue {C595} MODIFICATION: cysteine residue {C617} N-glycosylation site {N603} cysteine residue {C617} MODIFICATION: cysteine residue {C595} cysteine residue {C620} MODIFICATION: cysteine residue {C628} cysteine residue {C624} MODIFICATION: cysteine residue {C636} cysteine residue {C628} MODIFICATION: cysteine residue {C620} cysteine residue {C636} MODIFICATION: cysteine residue {C624} transmembrane domain {646-668} Thr phosphorylation site {T678} Thr phosphorylation site {T693} Ser phosphorylation site {S695} kinase domain SITE: 712-979 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 718-726 ATP-binding site NAME: ATP-binding site SITE: 745-745 aspartate residue {D837} Tyr phosphorylation site {Y869} Tyr phosphorylation site {Y978} Ser phosphorylation site {S991} Ser phosphorylation site {S995} Tyr phosphorylation site {Y998} tyrosine residue {1016} serine-rich region {1025-1071} MOTIF: serine residue (SEVERAL) Ser phosphorylation site {S1026} Ser phosphorylation site {S1064} Tyr phosphorylation site {Y1069} Ser phosphorylation site {S1070} Ser phosphorylation site {S1071} Tyr phosphorylation site {Y1092} Tyr phosphorylation site {Y1110} Tyr phosphorylation site {Y1138} Ser phosphorylation site {S1166} Tyr phosphorylation site {Y1172} Tyr phosphorylation site {Y1197}

Database Correlations

OMIM correlations MORBIDMAP 131550 UniProt P00533 PFAM correlations Entrez Gene 1956 KEGG correlations ENZYME 2.7.10.1

References

  1. UniProt :accession P00533
  2. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=EGFR
  3. Wikipedia; Note: EGFR entry http://en.wikipedia.org/wiki/epidermal_growth_factor_receptor
  4. Nishibe S et al Selectivity of phospholipase C phosphorylation by the epidermal growth factor receptor, the insulin receptor, and their cytoplasmic domains. Proc Natl Acad Sci U S A. 1990 Jan;87(1):424-8. Erratum in: Proc Natl Acad Sci U S A 1990 Apr;87(8):3253. Kim JJ [corrected to Kim JW]. PMID: 2153302
  5. Wang KK et al Calmodulin-binding proteins as calpain substrates. Biochem J 262:693 1989 PMID: 2556106
  6. Hollenberg MD. Structure-activity relationships for transmembrane signaling: the receptor's turn. FASEB J. 1991 Feb;5(2):178-86. Review. PMID: 1848518
  7. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 769
  8. Pawson T Protein modules and signalling networks Nature 373:573 1995 PMID: 7531822
  9. Kemp BE, Pearson RB. Protein kinase recognition sequence motifs. Trends Biochem Sci. 1990 Sep;15(9):342-6. Review. PMID: 2238044

Component-of

molecular complex