Egfr

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: This is the core molecular function of EGFR - a ligand-activated transmembrane receptor tyrosine kinase that transmits a signal across the plasma membrane by catalyzing tyrosine autophosphorylation. The IBA inference is phylogenetically sound for the EGF receptor subfamily. Reason: Core molecular function, well supported by family membership, domain architecture, and rat phosphoproteomic evidence of EGF-induced EGFR tyrosine phosphorylation. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md EGFR is a receptor protein-tyrosine kinase that increases intrinsic kinase activity upon ligand-induced dimerization and catalyzes autophosphorylation on cytoplasmic tyrosines, generating SH2/PTB docking sites for signaling proteins such as GRB2, GAB1, and PLCγ. file:rat/Egfr/Egfr-deep-research-falcon.md EGFR is a single-pass transmembrane receptor with an extracellular ligand-binding region containing cysteine-rich subdomains, a transmembrane helix, and an intracellular tyrosine kinase domain with a C-terminal phosphotyrosine tail for adaptor docking.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: EGFR is a single-pass type I plasma membrane receptor where ligand binding occurs outside the cell and kinase signaling occurs inside. This is the core site of its primary function. Reason: Core localization for a transmembrane receptor; consistent with UniProt cell membrane assignment and rat tissue evidence. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor (ligand binding outside the cell; kinase signaling inside), and it is internalized after activation.
GO:0043235 receptor complex	IBA GO_REF:0000033	ACCEPT	Summary: Activated EGFR functions as a dimer (homodimer or ErbB heterodimer), forming a signaling receptor complex. This is integral to the activation mechanism. Reason: EGFR signaling requires ligand-induced dimerization into a receptor complex; well supported. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md EGFR is activated by binding EGF-family ligands, which stabilizes an active extracellular conformation, exposes a dimerization interface, and promotes receptor dimerization.
GO:0030182 neuron differentiation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: EGFR signaling contributes to neuronal/glial differentiation in some contexts, but this is a downstream pleiotropic developmental outcome rather than the core biochemical function of the receptor. Reason: A downstream developmental process; valid but not part of the core receptor tyrosine kinase function.
GO:0043066 negative regulation of apoptotic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: EGFR-driven PI3K-AKT signaling promotes cell survival, which manifests as negative regulation of apoptosis. This is a downstream consequence of core signaling rather than the core function itself. Reason: Downstream survival effect of EGFR signaling; pleiotropic, not core.
GO:0043410 positive regulation of MAPK cascade	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: A defining downstream output of EGFR is activation of the RAS-RAF-MEK-ERK (MAPK) cascade via GRB2/SHC1 recruitment. This is one of the principal signaling consequences of receptor activation, but it is a downstream BP consequence of the core RTK activity rather than the core function itself. Reason: Direct downstream signaling pathway; well-supported in rat tissue phosphoproteomics, but represents a BP consequence of core RTK activity (which requires RAS/RAF/MEK/ERK, other gene products) rather than the core molecular function. Treated consistently with other downstream BP outcomes (apoptosis, proliferation) in this review. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md Autophosphorylation enables recruitment of adaptor/effector proteins (e.g., GRB2, GAB1, PLCγ), coupling EGFR to major signaling routes including RAS–RAF–MEK–ERK (MAPK) and PI3K–AKT–mTOR, among others. file:rat/Egfr/Egfr-deep-research-falcon.md In rat IMCD, EGF increases phosphorylation on EGFR tyrosines (e.g., Y1091/Y1171 in rat phosphoproteomics), consistent with enhanced kinase activity and generation of SH2-binding motifs that recruit adaptors such as Shc1 and Grb2 to couple EGFR to Ras and downstream MAPK signaling.
GO:0007173 epidermal growth factor receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: EGFR is the defining receptor of the epidermal growth factor receptor signaling pathway. This is a core biological process for the gene. Reason: Core biological process - EGFR is the namesake and central node of this pathway. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md In native rat IMCD, EGF stimulation produces phosphoproteomic signatures consistent with canonical ErbB signaling (Raf/MEK/ERK; PI3K-Akt; mTOR; endocytosis-associated networks), indicating that rat Egfr is embedded in the conserved EGFR signaling architecture in intact epithelial tissue.
GO:0050679 positive regulation of epithelial cell proliferation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: EGFR mitogenic signaling promotes epithelial cell proliferation. This is an important but downstream/pleiotropic consequence of core signaling rather than the core biochemical function. Reason: Downstream proliferative outcome of EGFR signaling; pleiotropic.
GO:0009925 basal plasma membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: In polarized epithelia EGFR localizes to the basal/basolateral plasma membrane. This is a context-specific refinement of plasma membrane localization rather than a distinct core function. Reason: Context-specific (polarized epithelial) localization refinement; supported by rat collecting duct evidence for the basolateral domain. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md In native rat IMCD, EGFR is reported at the basolateral plasma membrane, consistent with epithelial polarity and paracrine signaling in the collecting duct.
GO:0048408 epidermal growth factor binding	IBA GO_REF:0000033	ACCEPT	Summary: EGFR binds EGF-family ligands via its extracellular cysteine-rich domains; ligand binding is the obligatory first step of receptor activation. This is a core molecular function. Reason: Core molecular function - ligand recognition is intrinsic to receptor activation. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md EGFR is activated by binding EGF-family ligands, which stabilizes an active extracellular conformation, exposes a dimerization interface, and promotes receptor dimerization.
GO:0000166 nucleotide binding	IEA GO_REF:0000104	MARK AS OVER ANNOTATED	Summary: This is a generic parent of ATP binding. The informative molecular function is ATP binding (GO:0005524) in the kinase active site, which is separately annotated. Reason: Overly generic - subsumed by the more specific and directly relevant ATP binding annotation.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Generic parent of the specific transmembrane receptor protein tyrosine kinase activity (GO:0004714). EGFR is a tyrosine, not a generic protein, kinase. Reason: Overly generic; subsumed by the specific GO:0004714 / GO:0004713 tyrosine kinase annotations.
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: EGFR is a protein tyrosine kinase. This is correct but less specific than the transmembrane receptor protein tyrosine kinase activity (GO:0004714, a direct child of GO:0004713) that captures the receptor nature of EGFR and adds no information given GO:0004714. Reason: Overly generic; subsumed by and uninformative relative to the more specific GO:0004714 (its direct child), consistent with the treatment of the analogous generic parent GO:0004672 (protein kinase activity).
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IEA GO_REF:0000003	ACCEPT	Summary: Core molecular function (duplicate of the IBA-supported annotation above, from EC mapping). EGFR transmits a signal across the membrane by tyrosine kinase catalysis. Reason: Core molecular function; IEA from EC mapping corroborates the IBA annotation. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md EGFR catalyzes protein tyrosine phosphorylation on its own cytoplasmic tail (autophosphorylation) after ligand-induced activation.
GO:0005006 epidermal growth factor receptor activity	IEA GO_REF:0000117	ACCEPT	Summary: This is the most specific molecular function term for EGFR, capturing both EGF ligand recognition and the receptor tyrosine kinase activity. A core molecular function. Reason: Most specific and accurate MF term for this gene product. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md EGFR is a receptor protein-tyrosine kinase that increases intrinsic kinase activity upon ligand-induced dimerization and catalyzes autophosphorylation on cytoplasmic tyrosines, generating SH2/PTB docking sites for signaling proteins such as GRB2, GAB1, and PLCγ.
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: ATP binding in the kinase domain active site (residues 719-727, 746 per UniProt) is required for the phosphotransfer reaction. A supporting molecular function of the kinase activity. Reason: Directly supports the catalytic kinase function; ATP is the phosphate-donor substrate. Mapped to defined ATP-binding residues in UniProt.
GO:0005634 nucleus	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: A pool of EGFR can undergo noncanonical trafficking to the nucleus where it acts as a transcriptional co-activator. This is a real but non-core, context-dependent localization; the evidence here is not rat-specific. Reason: Noncanonical nuclear localization is documented in broader EGFR literature but is not the core plasma-membrane signaling function. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md additional noncanonical trafficking to ER/nuclear membranes and the nucleus has been described in broader EGFR literature.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: Core localization (duplicate of the IBA-supported plasma membrane annotation above, from UniProt subcellular location mapping). Reason: Core localization; IEA corroborates the IBA annotation.
GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: EGFR signaling is the prototypical cell surface receptor tyrosine kinase signaling pathway. This is a correct (more general) parent of the EGFR-specific pathway (GO:0007173), which is the preferred term and is separately annotated. Reason: Accurate but redundant with the more specific gene-specific EGFR signaling pathway (GO:0007173, ACCEPT); kept as non-core to signal that the child term is preferred.
GO:0009986 cell surface	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: EGFR is exposed at the cell surface, consistent with its plasma membrane receptor role. Supported by rat RGD IDA evidence in UniProt. Reason: Correct but largely redundant with the more precise plasma membrane annotation.
GO:0016020 membrane	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Generic membrane localization, subsumed by the specific plasma membrane annotation. Reason: Overly generic; the informative localization is plasma membrane.
GO:0016323 basolateral plasma membrane	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: In polarized epithelia (including rat collecting duct) EGFR localizes to the basolateral plasma membrane. A context-specific refinement of plasma membrane localization. Reason: Context-specific epithelial localization; supported by rat IMCD evidence but not the core localization for the gene generally. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md In native rat IMCD, EGFR is reported at the basolateral plasma membrane, consistent with epithelial polarity and paracrine signaling in the collecting duct.
GO:0021537 telencephalon development	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: EGFR signaling contributes to forebrain development in some contexts, but this specific developmental annotation from an ARBA ML model is a distal pleiotropic outcome, not a core function. Reason: Distal developmental process; pleiotropic and not core to EGFR biochemistry.
GO:0030139 endocytic vesicle	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: After ligand activation, EGFR is internalized by clathrin-mediated endocytosis into endocytic vesicles/endosomes, where it can continue signaling before recycling or degradation. A real, functionally important non-core localization. Reason: Trafficking-associated localization; modulates signal duration but is not the core plasma-membrane signaling site. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md ligand-activated EGFR undergoes clathrin-mediated endocytosis (CME) and can remain signaling-competent in early endosomes, with downstream signaling outputs shaped by whether receptors are recycled versus targeted to lysosomal degradation.
GO:0038134 ERBB2-EGFR signaling pathway	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: EGFR can heterodimerize with ERBB2/HER2 to form a potent signaling unit. This is one specific signaling configuration of EGFR rather than its core pathway. Reason: Specific heterodimer signaling configuration; a sub-aspect of EGFR signaling, not the core pathway by itself.
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: EGFR signaling is downregulated by Cbl/Cbl-b-mediated ubiquitination and receptor degradation, which feed back to limit signaling. EGFR participates in its own negative regulation through these trafficking/degradation routes. Reason: Self-limiting feedback (ubiquitin/degradation) is a regulatory aspect of EGFR biology, not its core activating function. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md Cbl-b preferentially engages EGFR via pY1045, whereas Cbl relies more strongly on a GRB2-dependent mechanism.
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Internalized EGFR accumulates in perinuclear endosomal compartments during trafficking. A trafficking-associated non-core localization. Reason: Trafficking-associated localization; not the core signaling site.
GO:0050679 positive regulation of epithelial cell proliferation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Duplicate (IEA) of the IBA epithelial proliferation annotation above; a downstream pleiotropic mitogenic outcome. Reason: Downstream proliferative outcome; pleiotropic, not core.
GO:0005515 protein binding	IPI PMID:30574069 Endocytic Adaptor Protein HIP1R Controls Intracellular Traff...	MARK AS OVER ANNOTATED	Summary: The generic protein binding term is uninformative about the actual function. The cited study concerns HIP1R-EGFR interaction in dendritic trafficking; the informative functions (receptor tyrosine kinase activity, EGF binding, receptor complex formation) are captured by more specific terms. Reason: Uninformative generic term; per curation guidelines avoid protein binding in favor of specific molecular functions, which are separately annotated.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:20639532 A novel role of CPEB3 in regulating EGFR gene transcription ...	ACCEPT	Summary: Direct experimental annotation of EGFR signaling pathway involvement (CPEB3/Stat5b regulation of EGFR in neurons). Core biological process, experimentally supported in rat neurons. Reason: Core biological process with direct experimental evidence in rat. Supporting Evidence: PMID:20639532 The elevated EGFR level in CPEB3 knockdown neurons, when stimulated with EGF, results in extended and amplified downstream signaling measured by phosphorylation of Stat5b and Akt.
GO:0007611 learning or memory	IDA PMID:20639532 A novel role of CPEB3 in regulating EGFR gene transcription ...	KEEP AS NON CORE	Summary: EGFR contributes to learning/memory in rat neurons via CPEB3-regulated expression. This is a distal pleiotropic, neuron-specific physiological outcome rather than the core receptor function. Reason: Distal physiological/behavioral outcome; pleiotropic, not core biochemistry, although experimentally supported.
GO:0071364 cellular response to epidermal growth factor stimulus	IDA PMID:20639532 A novel role of CPEB3 in regulating EGFR gene transcription ...	ACCEPT	Summary: EGFR is the receptor that mediates the cellular response to EGF, making this a core process directly tied to receptor function and supported by direct evidence. Reason: Core process - EGFR is the proximate transducer of the cellular EGF response. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md EGFR is a receptor protein-tyrosine kinase that increases intrinsic kinase activity upon ligand-induced dimerization and catalyzes autophosphorylation on cytoplasmic tyrosines, generating SH2/PTB docking sites for signaling proteins such as GRB2, GAB1, and PLCγ.

Gene Description

Existing Annotations Review

Core Functions

Ligand-activated transmembrane receptor tyrosine kinase - EGFR binds EGF-family ligands at the cell surface, dimerizes, and autophosphorylates C-terminal tyrosines via its intracellular kinase domain, transmitting the signal across the plasma membrane.

EGF-family ligand recognition - the extracellular cysteine-rich domains bind EGF, the obligatory first step that initiates receptor activation.

Initiation of EGFR signaling and downstream MAPK/PI3K activation - autophosphorylated EGFR recruits GRB2/SHC1/GAB1/PLCgamma to drive the RAS-RAF-MEK-ERK and PI3K-AKT-mTOR pathways.

References

Deep Research

Falcon

📚 Additional Documentation

Bioreason Rl Predictions

Bioreason Rl Review

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