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. Supporting Evidence: PMID:30574069 We found out that HIP1R interacts with EGFR and induces EGFR endocytosis to participate in dendritic development.
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. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md These pathways govern proliferation, growth, survival, motility, and context-dependent transcriptional programs.
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. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md These pathways govern proliferation, growth, survival, motility, and context-dependent transcriptional programs.
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	KEEP AS NON CORE	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: Correct but generic - subsumed by the more specific and directly relevant ATP binding annotation. Nothing in the term overshoots the evidence (the kinase domain binds ATP), so it is kept as a non-core parent rather than flagged as an over-annotation. Supporting Evidence: UniProtKB:G3V6K6 CATALYTIC ACTIVITY: Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
GO:0004672 protein kinase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Generic parent of the specific transmembrane receptor protein tyrosine kinase activity (GO:0004714). EGFR is a tyrosine, not a generic protein, kinase. Reason: Correct but generic; subsumed by the specific GO:0004714 / GO:0004713 tyrosine kinase annotations. EGFR does phosphorylate proteins, so the term does not overshoot the evidence and is kept as a non-core parent. Supporting Evidence: UniProtKB:G3V6K6 CATALYTIC ACTIVITY: Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) UniProtKB:G3V6K6 SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000002	KEEP AS NON CORE	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: Correct but 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). The term does not overshoot the evidence, so it is a non-core parent rather than an over-annotation. GOA no longer carries this InterPro2GO row; the same term returns via GO_REF:0000120 and is reviewed there as KEEP_AS_NON_CORE. Supporting Evidence: UniProtKB:G3V6K6 CATALYTIC ACTIVITY: Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
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. Supporting Evidence: UniProtKB:G3V6K6 CATALYTIC ACTIVITY: Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
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. Supporting Evidence: UniProtKB:G3V6K6 SUBCELLULAR LOCATION: Cell membrane 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: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. 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: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, binding extracellular EGF-family ligands. Reason: Correct but largely redundant with the more precise plasma membrane annotation. 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:0016020 membrane	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Generic membrane localization, subsumed by the specific plasma membrane annotation. Reason: Correct but generic; the informative localization is plasma membrane. The term does not overshoot the evidence for a single-pass transmembrane receptor, so it is kept as a non-core parent. Supporting Evidence: UniProtKB:G3V6K6 SUBCELLULAR LOCATION: Cell 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. Supporting Evidence: PMID:30574069 In CNS, EGF and EGFR are expressed in brain regions including cortex, hippocampus and cerebellum during development and also in adulthood
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. 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: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. 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: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. Supporting Evidence: file:rat/Egfr/Egfr-deep-research-falcon.md These pathways govern proliferation, growth, survival, motility, and context-dependent transcriptional programs.
GO:0005515 protein binding	IPI PMID:30574069 Endocytic Adaptor Protein HIP1R Controls Intracellular Traff...	REMOVE	Summary: IPI with mouse HIP1R (Q9JKY5) from a study of EGFR endocytosis in cultured rat hippocampal neurons. HIP1R is the endocytic adaptor and EGFR the cargo it internalizes; the paper does not define an EGFR molecular activity beyond being bound, and the informative EGFR functions (receptor tyrosine kinase activity, EGF binding, receptor complex) are captured by other rows. Reason: Generic protein binding is uninformative, and no more specific EGFR MF term is supported by this interaction (the adaptor activity belongs to HIP1R). Removal does not mean the HIP1R-EGFR interaction is false; the interaction is better represented on HIP1R or in EGFR trafficking process terms. Supporting Evidence: PMID:30574069 We found out that HIP1R interacts with EGFR and induces EGFR endocytosis to participate in dendritic development.
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. Supporting Evidence: PMID:20639532 activation or deprivation of EGFR’s kinase activity by infusing EGF or gefitinib (23), respectively, in the brain, affects spatial learning and memory performance in mice.
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: 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. 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:0000139 Golgi membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular-location mapping (ARBA) to Golgi membrane. As a single- pass type I glycoprotein, EGFR transits the Golgi on the biosynthetic route to the cell surface; the Golgi is a transit compartment, not a site of EGFR signalling function. Reason: Correct as a biosynthetic transit location for a glycosylated cell-surface receptor, but not where EGFR acts; non-core. Supporting Evidence: UniProtKB:G3V6K6 Golgi apparatus membrane 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:0004713 protein tyrosine kinase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Combined-IEA annotation to protein tyrosine kinase activity. EGFR catalyses tyrosine phosphorylation (UniProt catalytic activity, EC 2.7.10.1); the term is correct but is the parent of the more specific transmembrane receptor protein tyrosine kinase activity (GO:0004714) annotated by IBA and IEA. Reason: Accurate but less specific than GO:0004714, which is the core MF; kept as a non-core parent. Same term as the retired InterPro2GO row, now supplied by GO_REF:0000120. Supporting Evidence: UniProtKB:G3V6K6 CATALYTIC ACTIVITY: Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) UniProtKB:G3V6K6 SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular-location mapping (ARBA) to endoplasmic reticulum membrane. EGFR is synthesised and folded in the ER, and retrograde trafficking of activated EGFR to the ER/nuclear envelope has been described in non-rat systems. Reason: Plausible biosynthetic and noncanonical trafficking location, not the core signalling site; no rat-specific evidence for functional ER-resident EGFR. Supporting Evidence: UniProtKB:G3V6K6 Endoplasmic reticulum membrane file:rat/Egfr/Egfr-deep-research-falcon.md Broader EGFR literature also supports additional intracellular routes (e.g., trafficking to ER/nuclear membranes and nuclear import) where EGFR can function as a transcriptional co-activator
GO:0010008 endosome membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular-location mapping (ARBA) to endosome membrane. Ligand- activated EGFR is internalised by clathrin-mediated endocytosis and can continue to signal from early endosomes before recycling or lysosomal degradation. Reason: Well-established trafficking location that shapes signal duration; consistent with the endocytic vesicle row, but the core signalling site is the plasma membrane. Supporting Evidence: UniProtKB:G3V6K6 Endosome membrane 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:0016301 kinase activity	IEA GO_REF:0000104	KEEP AS NON CORE	Summary: UniRule-based IEA to the generic kinase activity term. EGFR is a protein tyrosine kinase, so the term is true but uninformative relative to GO:0004714. Reason: Correct but generic grouping term; the informative MF is transmembrane receptor protein tyrosine kinase activity. Nothing overshoots the evidence, so it is kept as a non-core parent. Supporting Evidence: UniProtKB:G3V6K6 CATALYTIC ACTIVITY: Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
GO:0016740 transferase activity	IEA GO_REF:0000104	KEEP AS NON CORE	Summary: UniRule-based IEA to transferase activity, the top-level class containing kinases. EGFR transfers phosphate from ATP to tyrosine, so the term is true but minimally informative. Reason: Correct but very generic; the informative MF is transmembrane receptor protein tyrosine kinase activity. Kept as a non-core parent. Supporting Evidence: UniProtKB:G3V6K6 CATALYTIC ACTIVITY: Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
GO:0031965 nuclear membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular-location mapping (ARBA) to nuclear membrane. Noncanonical trafficking of EGFR to the nuclear envelope and nucleus has been described in the broader (largely non-rat, often cancer-cell) EGFR literature. Reason: Context-dependent noncanonical location, consistent with the non-core nucleus row; not the core plasma-membrane signalling site. Supporting Evidence: UniProtKB:G3V6K6 Nucleus membrane file:rat/Egfr/Egfr-deep-research-falcon.md Broader EGFR literature also supports additional intracellular routes (e.g., trafficking to ER/nuclear membranes and nuclear import) where EGFR can function as a transcriptional co-activator

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

Notes

Bioreason Rl Predictions

Bioreason Rl Review

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