Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Egfr. (This text reflects annotations as of Thursday, July 24, 2014.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Egfr
  • participates in the following biological processes:
    • cellular response to amino acid stimulus ^[22]
    • epidermal growth factor receptor signaling pathway ^{[14, 23]}
    • peptidyl-tyrosine phosphorylation ^[23]
    • positive regulation of cell proliferation ^[23]
    • protein autophosphorylation ^[6]
    • signal transduction ^[18]
  • performs the following molecular functions:
    • epidermal growth factor-activated receptor activity ^[23]
    • kinase activity ^[8]
    • signal transducer activity ^[18]
  • is located in the following cellular components:
    • basolateral plasma membrane ^[15]
    • endocytic vesicle ^[12]
    • intracellular ^[12]
    • nucleus ^[17]
    • perinuclear region of cytoplasm ^[17]
    • plasma membrane ^[7]
• The gene product of Egfr has been shown to bind to the gene products of Caml, Cbl, Kras, Lingo1, Src, Usp8. ^{[1, 2, 3, 9, 11, 13, 14, 19, 21]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Egfr
  • participates in the following biological processes:
    • cerebral cortex cell migration ^[20]
    • digestive tract morphogenesis ^[20]
    • embryonic placenta development ^[20]
    • epidermal growth factor receptor signaling pathway ^[4]
    • epidermis development ^[20]
    • hair follicle development ^[20]
    • morphogenesis of an epithelial fold ^[20]
    • positive regulation of epithelial cell proliferation ^[20]
    • positive regulation of fibroblast proliferation ^[17]
    • regulation of peptidyl-tyrosine phosphorylation ^[18]
    • salivary gland morphogenesis ^[10]
• Researchers have inferred, based on genetic interactions, that the gene product of Egfr
  • participates in the following biological processes:
    • cell morphogenesis based on interactions with Ss18 ^[4]
    • epidermal growth factor receptor signaling pathway based on interactions with Egf ^[7]
    • positive regulation of cell proliferation based on interactions with Apc, B4galt1, Btc, Egf ^{[5, 7]}
    • regulation of cell proliferation based on interactions with Apc ^[16]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Egfr:
  • participates in the following biological processes:
    • activation of MAPKK activity
    • astrocyte activation
    • cell proliferation
    • cell surface receptor signaling pathway
    • cellular response to epidermal growth factor stimulus
    • cellular response to estradiol stimulus
    • epidermal growth factor receptor signaling pathway
    • intracellular signal transduction
    • learning or memory
    • magnesium ion homeostasis
    • negative regulation of apoptotic process
    • negative regulation of mitotic cell cycle
    • negative regulation of protein catabolic process
    • neuron projection morphogenesis
    • ovulation cycle
    • peptidyl-tyrosine phosphorylation
    • positive regulation of catenin import into nucleus
    • positive regulation of cell migration
    • positive regulation of cell proliferation
    • positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
    • positive regulation of DNA repair
    • positive regulation of DNA replication
    • positive regulation of epithelial cell proliferation
    • positive regulation of ERK1 and ERK2 cascade
    • positive regulation of inflammatory response
    • positive regulation of MAP kinase activity
    • positive regulation of nitric oxide biosynthetic process
    • positive regulation of phosphorylation
    • positive regulation of protein kinase B signaling
    • positive regulation of protein phosphorylation
    • positive regulation of smooth muscle cell proliferation
    • positive regulation of superoxide anion generation
    • positive regulation of synaptic transmission, glutamatergic
    • positive regulation of transcription from RNA polymerase II promoter
    • positive regulation of vasoconstriction
    • positive regulation of vasodilation
    • protein autophosphorylation
    • regulation of nitric-oxide synthase activity
    • regulation of peptidyl-tyrosine phosphorylation
    • response to calcium ion
    • response to UV-A
    • signal transduction
    • single organismal cell-cell adhesion
    • translation
  • performs the following molecular functions:
    • actin filament binding
    • chromatin binding
    • enzyme binding
    • epidermal growth factor binding
    • epidermal growth factor-activated receptor activity
    • glycoprotein binding
    • identical protein binding
    • integrin binding
    • nitric-oxide synthase regulator activity
    • protein heterodimerization activity
    • protein kinase binding
    • protein phosphatase binding
    • protein tyrosine kinase activity
    • receptor binding
    • transmembrane signaling receptor activity
  • is located in the following cellular components:
    • apical plasma membrane
    • basolateral plasma membrane
    • cell surface
    • cytoplasm
    • endocytic vesicle
    • endosome
    • membrane
    • membrane raft
    • nucleus
    • plasma membrane
    • receptor complex

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Summary text based on GO annotations supported by structural data

• Egfr encodes a protein or proteins that contain the following InterPro domains: EGF receptor, L domain, Furin-like cysteine-rich domain, Furin-like repeat, Insulin-like growth factor binding protein, N-terminal, Protein kinase, ATP binding site, Protein kinase, catalytic domain, Protein kinase-like domain, Serine-threonine/tyrosine-protein kinase catalytic domain, Tyrosine protein kinase, EGF/ERB/XmrK receptor, Tyrosine-protein kinase, active site, Tyrosine-protein kinase, catalytic domain, indicating that the gene product:
  • participates in the following biological processes:
    • protein phosphorylation
    • transmembrane receptor protein tyrosine kinase signaling pathway
  • performs the following molecular functions:
    • ATP binding
    • protein kinase activity
    • receptor signaling protein tyrosine kinase activity
    • transferase activity, transferring phosphorus-containing groups
    • transmembrane receptor protein tyrosine kinase activity
  • is located in the following cellular components:
    • integral component of membrane

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Egfr indicates that it:
  • participates in the following biological processes:
    • multicellular organismal development
    • phosphorylation
  • performs the following molecular functions:
    • ATP binding
    • nucleotide binding
    • transferase activity
  • is located in the following cellular components:
    • endoplasmic reticulum
    • Golgi apparatus
    • integral component of membrane
• Egfr has been associated with the Enzyme Commission numbers: 2.7.10.1, which implies that the gene product:
  • performs the following molecular functions:
    • transmembrane receptor protein tyrosine kinase activity

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References

1. Andreev J et al. (2001) Src and Pyk2 mediate G-protein-coupled receptor activation of epidermal growth factor receptor (EGFR) but are not required for coupling to the mitogen-activated protein (MAP) kinase signaling cascade. J Biol Chem, 276:20130-5. (PubMed:11274221)
2. Aoki K et al. (2005) Local phosphatidylinositol 3,4,5-trisphosphate accumulation recruits Vav2 and Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth factor-stimulated PC12 cells. Mol Biol Cell, 16:2207-17. (PubMed:15728722)
3. Ardito CM et al. (2012) EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell, 22:304-17. (PubMed:22975374)
4. Barco R et al. (2007) The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskeleton through activation of the ephrin pathway. Mol Biol Cell, 18:4003-12. (PubMed:17686994)
5. Dahlhoff M et al. (2008) Betacellulin stimulates growth of the mouse intestinal epithelium and increases adenoma multiplicity in Apc(+/Min) mice. FEBS Lett, 582:2911-5. (PubMed:18656477)
6. Higuchi T et al. (2004) MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met. Mol Cell Biol, 24:7456-68. (PubMed:15314156)
7. Hinton DA et al. (1995) Altering the expression of cell surface beta 1,4-galactosyltransferase modulates cell growth. Exp Cell Res, 219:640-9. (PubMed:7641815)
8. Holgado-Madruga M et al. (2003) Gab1 is an integrator of cell death versus cell survival signals in oxidative stress. Mol Cell Biol, 23:4471-84. (PubMed:12808090)
9. Inoue H et al. (2007) Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models. Proc Natl Acad Sci U S A, 104:14430-5. (PubMed:17726113)
10. Jaskoll T et al. (1999) Submandibular gland morphogenesis: stage-specific expression of TGF-alpha/EGF, IGF, TGF-beta, TNF, and IL-6 signal transduction in normal embryonic mice and the phenotypic effects of TGF-beta2, TGF-beta3, and EGF-r null mutations. Anat Rec, 256:252-68. (PubMed:10521784)
11. Lahti JL et al. (2011) Engineered epidermal growth factor mutants with faster binding on-rates correlate with enhanced receptor activation. FEBS Lett, 585:1135-9. (PubMed:21439278)
12. Mikkola ML et al. (1999) Ectodysplasin, a protein required for epithelial morphogenesis, is a novel TNF homologue and promotes cell-matrix adhesion. Mech Dev, 88:133-46. (PubMed:10534613)
13. Mizuno E et al. (2005) Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes. Mol Biol Cell, 16:5163-74. (PubMed:16120644)
14. Nicholson SE et al. (2005) Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling. Proc Natl Acad Sci U S A, 102:2328-33. (PubMed:15695332)
15. Orellana SA et al. (1995) Epidermal growth factor receptor expression is abnormal in murine polycystic kidney. Kidney Int, 47:490-9. (PubMed:7723235)
16. Roberts RB et al. (2002) Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. Proc Natl Acad Sci U S A, 99:1521-6. (PubMed:11818567)
17. Rocher-Ros V et al. (2010) Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7. Oncogene, 29:2950-61. (PubMed:20208556)
18. Saito Y et al. (2002) Protein kinase C-alpha and protein kinase C-epsilon are required for Grb2-associated binder-1 tyrosine phosphorylation in response to platelet-derived growth factor. J Biol Chem, 277:23216-22. (PubMed:11940581)
19. Sigismund S et al. (2013) Threshold-controlled ubiquitination of the EGFR directs receptor fate. EMBO J, 32:2140-57. (PubMed:23799367)
20. Threadgill DW et al. (1995) Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science, 269:230-4. (PubMed:7618084)
21. Tran DD et al. (2003) CAML is required for efficient EGF receptor recycling. Dev Cell, 5:245-56. (PubMed:12919676)
22. Wang CF et al. (2012) Calpain 2 Activated through N-Methyl-D-Aspartic Acid Receptor Signaling Cleaves CPEB3 and Abrogates CPEB3-Repressed Translation in Neurons. Mol Cell Biol, 32:3321-32. (PubMed:22711986)
23. Weissman JT et al. (2004) G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway. Oncogene, 23:241-9. (PubMed:14712229)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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