Egfr

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0043235 receptor complex	IBA GO_REF:0000033	ACCEPT	Summary: Active EGFR exists as a ligand-induced homo- or heterodimeric receptor complex (e.g. with ERBB2), the signaling-competent unit. Reason: Captures the functional dimeric receptor assembly; core CC supported by IBA/ISO. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0030182 neuron differentiation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: EGFR contributes to neuronal differentiation in the nervous system. Reason: Developmental role downstream of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:0043066 negative regulation of apoptotic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: EGFR-PI3K-AKT signaling promotes cell survival by suppressing apoptosis, e.g. in keratinocytes. Reason: Pro-survival downstream effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0043410 positive regulation of MAPK cascade	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phosphorylated EGFR recruits GRB2/SOS to activate the RAS-RAF-MEK-ERK MAPK cascade. Reason: Major downstream signaling output, but a regulatory effect downstream of the receptor's own activity. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0007173 epidermal growth factor receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0050679 positive regulation of epithelial cell proliferation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: EGFR drives proliferation of epithelial cells, central to epithelial development and homeostasis. Reason: Cell-type-specific proliferative effect downstream of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0009925 basal plasma membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: In polarized epithelial cells EGFR is found at the basal plasma-membrane domain. Reason: Polarity-specific subdomain; non-core specialization of plasma membrane. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0048408 epidermal growth factor binding	IBA GO_REF:0000033	ACCEPT	Summary: The EGFR extracellular L-domains directly bind EGF and other EGF-family ligands, the event that triggers receptor dimerization and activation. Reason: Core ligand-binding MF supported by IDA; central to receptor function. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0000139 Golgi membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: As a single-pass membrane protein EGFR is found on Golgi membranes during transit. Reason: Secretory-pathway localization, secondary to surface signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	MODIFY	Summary: EGFR is a protein kinase, but specifically a transmembrane receptor tyrosine kinase; the bare parent term is uninformative for this receptor. Reason: Generic parent for a receptor tyrosine kinase; replace with the specific RTK MF term. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IEA GO_REF:0000003	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: EGFR's kinase domain binds ATP (residues 720-728, 747, 792-793, 857) as the phosphate donor for tyrosine phosphorylation. Reason: Required cofactor binding for the catalytic MF; correct and core despite IEA evidence. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005634 nucleus	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: A pool of EGFR translocates to the nucleus (via Golgi/ER, aided by PIKFYVE) where it can influence transcription in specific contexts. Reason: Context-specific non-canonical localization, secondary to membrane signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005768 endosome	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Activated EGFR is endocytosed into endosomes from which it can continue signaling before recycling or lysosomal degradation. Reason: Secondary localization arising from receptor trafficking, downstream of surface signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Nascent EGFR transits the ER membrane during biosynthesis, and retrograde Golgi-to-ER transport routes a nuclear pool. Reason: Biosynthetic/retrograde compartment, secondary to the receptor's signaling role. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway	IEA GO_REF:0000002	MODIFY	Summary: EGFR signals as a cell-surface receptor tyrosine kinase, but for this gene the specific EGFR signaling pathway term is the precise descriptor. Reason: Correct but generic parent pathway; replace with the EGFR-specific signaling pathway term. Proposed replacements: epidermal growth factor receptor signaling pathway Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0010008 endosome membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Internalized EGFR associates with endosomal membranes during its post-activation trafficking and downregulation. Reason: Secondary trafficking-derived localization, not the primary functional site. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0016020 membrane	IEA GO_REF:0000120	MODIFY	Summary: EGFR is a membrane protein, but the unqualified 'membrane' CC is uninformative when its plasma-membrane localization is established. Reason: Over-general CC parent; replace with plasma membrane. Proposed replacements: plasma membrane Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0021537 telencephalon development	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: EGFR contributes to telencephalon (forebrain) development. Reason: Developmental role downstream of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0030139 endocytic vesicle	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Ligand-activated EGFR is captured in endocytic vesicles during clathrin-mediated internalization. Reason: Trafficking-intermediate localization downstream of activation at the surface. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0031965 nuclear membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Nuclear-translocated EGFR is associated with the nuclear membrane as a single-pass membrane protein. Reason: Specialized non-canonical localization, not core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: EGFR signaling is subject to feedback downregulation (CBL-mediated ubiquitination, endocytosis, LRIG1/ERRFI1/SOCS feedback inhibitors). Reason: Regulatory/feedback process on its own pathway, supported by IDA/IMP but non-core to the receptor's MF. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:0005515 protein binding	IPI PMID:16954185 Advanced glycation end product (AGE) receptor 1 suppresses c...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0005515 protein binding	IPI PMID:21439278 Engineered epidermal growth factor mutants with faster bindi...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0005515 protein binding	IPI PMID:22975374 EGF receptor is required for KRAS-induced pancreatic tumorig...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0005515 protein binding	IPI PMID:23799367 Threshold-controlled ubiquitination of the EGFR directs rece...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0003682 chromatin binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Nuclear EGFR has been reported to bind chromatin and act as a transcriptional co-regulator in specific contexts. Reason: Non-canonical activity of the nuclear pool, downstream of canonical signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:0004888 transmembrane signaling receptor activity	IEA GO_REF:0000107	MODIFY	Summary: EGFR is a transmembrane signaling receptor, but more precisely a receptor tyrosine kinase that couples ligand binding to intrinsic catalytic activity. Reason: Correct but too general a receptor MF; replace with the kinase-coupled RTK term capturing the catalytic mechanism. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005006 epidermal growth factor receptor activity	IEA GO_REF:0000120	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005737 cytoplasm	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Internalized/trafficking EGFR and its cytoplasmic kinase domain are detected in the cytoplasmic compartment. Reason: Broad secondary localization, downstream of membrane localization. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005794 Golgi apparatus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR passes through the Golgi during maturation and in retrograde trafficking toward the nucleus. Reason: Biosynthetic/secretory pathway compartment, not the primary functional site. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0007165 signal transduction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: EGFR is a signal transducer, but this top-level process term is uninformative when the specific EGFR signaling pathway is annotated. Reason: Over-general process parent; specific EGFR signaling pathway captured separately. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0007173 epidermal growth factor receptor signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0009986 cell surface	IEA GO_REF:0000120	ACCEPT	Summary: EGFR is displayed at the cell surface where it encounters extracellular EGF-family ligands. Reason: Primary surface localization supported by IDA; core. Retain over the REMOVE-tagged duplicate. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0016323 basolateral plasma membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: EGFR localizes to the basolateral surface of polarized epithelia, consistent with its role in epithelial signaling. Reason: Polarity-specific subdomain of the primary localization, supported by IDA but non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0019899 enzyme binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: EGFR binds numerous enzymes (kinases, phosphatases, ligases), but 'enzyme binding' is a generic catch-all conveying no specific function. Reason: Uninformative parent binding term; specific enzyme interactions captured elsewhere. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0019900 kinase binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: EGFR interacts with kinases within signaling complexes, but 'kinase binding' is a generic uninformative term. Reason: Uninformative binding term, redundant with protein kinase binding. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0019903 protein phosphatase binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: EGFR is bound and dephosphorylated by phosphatases (PTPN1/2/6, PTPRJ/K), but the generic binding term does not specify this regulatory relationship. Reason: Uninformative MF term; the regulatory relationship is captured in process terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0030054 cell junction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR is detected at epithelial cell junctions where it intersects adhesion signaling. Reason: Specialized localization linked to adhesion, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0030296 protein tyrosine kinase activator activity	IEA GO_REF:0000107	MODIFY	Summary: EGFR's intrinsic activity is that of a tyrosine kinase, not an activator of another tyrosine kinase; the IEA term mis-types its function. Reason: Activator-activity framing is wrong-essence for the receptor itself; replace with its true RTK MF term. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0030307 positive regulation of cell growth	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling promotes cell growth (mass increase) in responsive cells. Reason: Downstream growth effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0030335 positive regulation of cell migration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR (via CCDC88A/GIV and cytoskeletal remodeling) promotes cell migration, important in wound healing. Reason: Downstream motility effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0031625 ubiquitin protein ligase binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Activated EGFR binds CBL/CBLB and other E3 ligases (RNF115, RNF126) that ubiquitinate it for endosomal sorting and degradation. Reason: Real interaction central to receptor downregulation, but a regulatory partner binding rather than the core MF. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:0031901 early endosome membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: After ligand-induced internalization EGFR resides on early endosome membranes, where sorting decisions (recycle vs degrade) shape signal duration. Reason: Real post-activation trafficking compartment downstream of plasma-membrane signaling; not the primary site. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0032587 ruffle membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Activated EGFR localizes to membrane ruffles during EGF-stimulated cytoskeletal remodeling and migration. Reason: Migration-associated membrane subdomain, secondary to signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0032991 protein-containing complex	IEA GO_REF:0000107	MODIFY	Summary: EGFR is part of signaling complexes, but the bare 'protein-containing complex' CC term is too generic; the receptor complex term is appropriate. Reason: Over-general cellular component; replace with receptor complex. Proposed replacements: receptor complex Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0034165 positive regulation of toll-like receptor 9 signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR can positively regulate TLR9 signaling in immune/inflammatory contexts. Reason: Pathway cross-talk effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0038134 ERBB2-EGFR signaling pathway	IEA GO_REF:0000120	ACCEPT	Summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling. Reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0042177 negative regulation of protein catabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling can stabilize partner proteins, negatively regulating their catabolism. Reason: Indirect downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0042327 positive regulation of phosphorylation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling increases phosphorylation of numerous downstream substrates. Reason: Broad downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0042802 identical protein binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: EGFR homodimerizes, but the generic 'identical protein binding' term does not capture the receptor-dimerization mechanism meaningfully. Reason: Generic term; dimerization is better captured by receptor complex/receptor-activity terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0043066 negative regulation of apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR-PI3K-AKT signaling promotes cell survival by suppressing apoptosis, e.g. in keratinocytes. Reason: Pro-survival downstream effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0043235 receptor complex	IEA GO_REF:0000107	ACCEPT	Summary: Active EGFR exists as a ligand-induced homo- or heterodimeric receptor complex (e.g. with ERBB2), the signaling-competent unit. Reason: Captures the functional dimeric receptor assembly; core CC supported by IBA/ISO. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0043410 positive regulation of MAPK cascade	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Phosphorylated EGFR recruits GRB2/SOS to activate the RAS-RAF-MEK-ERK MAPK cascade. Reason: Major downstream signaling output, but a regulatory effect downstream of the receptor's own activity. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR engages PI3K to activate AKT, a major pro-survival arm of its signaling. Reason: Downstream effector pathway, non-core relative to receptor activity. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0045121 membrane raft	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR partitions into membrane rafts/nanodomains that modulate its ligand binding and dimerization. Reason: Regulatory membrane subdomain; refinement of plasma-membrane localization, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0045739 positive regulation of DNA repair	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling can enhance DNA repair responses in some contexts. Reason: Downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0045740 positive regulation of DNA replication	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Mitogenic EGFR signaling promotes DNA replication during proliferation. Reason: Downstream proliferative effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0045944 positive regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling (and nuclear EGFR) promotes Pol II transcription of target genes. Reason: Downstream transcriptional output of signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Endosomal and Golgi-associated EGFR accumulates in the perinuclear region during trafficking. Reason: Trafficking-derived localization, secondary to surface signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0050679 positive regulation of epithelial cell proliferation	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: EGFR drives proliferation of epithelial cells, central to epithelial development and homeostasis. Reason: Cell-type-specific proliferative effect downstream of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0051015 actin filament binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR connects to the actin cytoskeleton during migration/ruffle formation, reported as actin filament binding. Reason: Real cytoskeletal association supporting migration, but downstream of core kinase signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR activation positively drives the PI3K-AKT survival pathway. Reason: Downstream regulatory effect of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0070141 response to UV-A	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: UV-A can transactivate EGFR (ligand-independent activation), linking it to UV stress responses. Reason: Stimulus-response role; transactivation context, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
GO:0070374 positive regulation of ERK1 and ERK2 cascade	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling activates the ERK1/2 (MAPK) cascade driving proliferative gene expression. Reason: Downstream effector cascade activation, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0071392 cellular response to estradiol stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR participates in cellular responses to estradiol, partly via GPER1-dependent transactivation. Reason: Stimulus-response role, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
GO:0090037 positive regulation of protein kinase C signaling	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Via PLCgamma activation EGFR drives PKC signaling. Reason: Downstream effector arm, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0090263 positive regulation of canonical Wnt signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling can positively modulate canonical Wnt signaling via cross-talk. Reason: Pathway cross-talk effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0097489 multivesicular body, internal vesicle lumen	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR sorted for degradation is delivered into the internal vesicles of multivesicular bodies via the ESCRT machinery. Reason: Degradation-pathway localization downstream of activation, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0097708 intracellular vesicle	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR is found in intracellular vesicles of the endocytic/trafficking system after internalization. Reason: Generic trafficking compartment, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0098609 cell-cell adhesion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR intersects cell-cell adhesion through cross-talk with junctional and adhesion molecules. Reason: Adhesion-related role downstream of/parallel to signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:1902895 positive regulation of miRNA transcription	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling promotes transcription of specific miRNAs. Reason: Downstream transcriptional effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:1903078 positive regulation of protein localization to plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling promotes recruitment/retention of partner proteins at the plasma membrane. Reason: Downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:1905208 negative regulation of cardiocyte differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: EGFR signaling negatively regulates cardiomyocyte differentiation during heart development. Reason: Cardiac developmental role downstream of signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0001934 positive regulation of protein phosphorylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Active EGFR promotes phosphorylation of effector proteins in its signaling network. Reason: Broad downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0003682 chromatin binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Nuclear EGFR has been reported to bind chromatin and act as a transcriptional co-regulator in specific contexts. Reason: Non-canonical activity of the nuclear pool, downstream of canonical signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:0004713 protein tyrosine kinase activity	ISO GO_REF:0000119	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005006 epidermal growth factor receptor activity	ISO GO_REF:0000119	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005634 nucleus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: A pool of EGFR translocates to the nucleus (via Golgi/ER, aided by PIKFYVE) where it can influence transcription in specific contexts. Reason: Context-specific non-canonical localization, secondary to membrane signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005737 cytoplasm	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Internalized/trafficking EGFR and its cytoplasmic kinase domain are detected in the cytoplasmic compartment. Reason: Broad secondary localization, downstream of membrane localization. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005768 endosome	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Activated EGFR is endocytosed into endosomes from which it can continue signaling before recycling or lysosomal degradation. Reason: Secondary localization arising from receptor trafficking, downstream of surface signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005794 Golgi apparatus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR passes through the Golgi during maturation and in retrograde trafficking toward the nucleus. Reason: Biosynthetic/secretory pathway compartment, not the primary functional site. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005886 plasma membrane	ISO GO_REF:0000119	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0007165 signal transduction	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: EGFR is a signal transducer, but this top-level process term is uninformative when the specific EGFR signaling pathway is annotated. Reason: Over-general process parent; specific EGFR signaling pathway captured separately. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0007173 epidermal growth factor receptor signaling pathway	ISO GO_REF:0000119	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0008284 positive regulation of cell population proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR is a mitogenic receptor driving proliferation of many cell types. Reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0009986 cell surface	ISO GO_REF:0000119	ACCEPT	Summary: EGFR is displayed at the cell surface where it encounters extracellular EGF-family ligands. Reason: Primary surface localization supported by IDA; core. Retain over the REMOVE-tagged duplicate. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0010008 endosome membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Internalized EGFR associates with endosomal membranes during its post-activation trafficking and downregulation. Reason: Secondary trafficking-derived localization, not the primary functional site. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0016020 membrane	ISO GO_REF:0000119	MODIFY	Summary: EGFR is a membrane protein, but the unqualified 'membrane' CC is uninformative when its plasma-membrane localization is established. Reason: Over-general CC parent; replace with plasma membrane. Proposed replacements: plasma membrane Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0016323 basolateral plasma membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR localizes to the basolateral surface of polarized epithelia, consistent with its role in epithelial signaling. Reason: Polarity-specific subdomain of the primary localization, supported by IDA but non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0019899 enzyme binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: EGFR binds numerous enzymes (kinases, phosphatases, ligases), but 'enzyme binding' is a generic catch-all conveying no specific function. Reason: Uninformative parent binding term; specific enzyme interactions captured elsewhere. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0019900 kinase binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: EGFR interacts with kinases within signaling complexes, but 'kinase binding' is a generic uninformative term. Reason: Uninformative binding term, redundant with protein kinase binding. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0019903 protein phosphatase binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: EGFR is bound and dephosphorylated by phosphatases (PTPN1/2/6, PTPRJ/K), but the generic binding term does not specify this regulatory relationship. Reason: Uninformative MF term; the regulatory relationship is captured in process terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0030054 cell junction	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR is detected at epithelial cell junctions where it intersects adhesion signaling. Reason: Specialized localization linked to adhesion, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0030307 positive regulation of cell growth	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling promotes cell growth (mass increase) in responsive cells. Reason: Downstream growth effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0030335 positive regulation of cell migration	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR (via CCDC88A/GIV and cytoskeletal remodeling) promotes cell migration, important in wound healing. Reason: Downstream motility effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0031625 ubiquitin protein ligase binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Activated EGFR binds CBL/CBLB and other E3 ligases (RNF115, RNF126) that ubiquitinate it for endosomal sorting and degradation. Reason: Real interaction central to receptor downregulation, but a regulatory partner binding rather than the core MF. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:0031901 early endosome membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: After ligand-induced internalization EGFR resides on early endosome membranes, where sorting decisions (recycle vs degrade) shape signal duration. Reason: Real post-activation trafficking compartment downstream of plasma-membrane signaling; not the primary site. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0032587 ruffle membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Activated EGFR localizes to membrane ruffles during EGF-stimulated cytoskeletal remodeling and migration. Reason: Migration-associated membrane subdomain, secondary to signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0032991 protein-containing complex	ISO GO_REF:0000119	MODIFY	Summary: EGFR is part of signaling complexes, but the bare 'protein-containing complex' CC term is too generic; the receptor complex term is appropriate. Reason: Over-general cellular component; replace with receptor complex. Proposed replacements: receptor complex Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0033138 positive regulation of peptidyl-serine phosphorylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling (via downstream Ser/Thr kinases) increases peptidyl-serine phosphorylation of targets. Reason: Indirect downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0042177 negative regulation of protein catabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling can stabilize partner proteins, negatively regulating their catabolism. Reason: Indirect downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0042327 positive regulation of phosphorylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling increases phosphorylation of numerous downstream substrates. Reason: Broad downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0042802 identical protein binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: EGFR homodimerizes, but the generic 'identical protein binding' term does not capture the receptor-dimerization mechanism meaningfully. Reason: Generic term; dimerization is better captured by receptor complex/receptor-activity terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0043066 negative regulation of apoptotic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR-PI3K-AKT signaling promotes cell survival by suppressing apoptosis, e.g. in keratinocytes. Reason: Pro-survival downstream effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0043410 positive regulation of MAPK cascade	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Phosphorylated EGFR recruits GRB2/SOS to activate the RAS-RAF-MEK-ERK MAPK cascade. Reason: Major downstream signaling output, but a regulatory effect downstream of the receptor's own activity. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR engages PI3K to activate AKT, a major pro-survival arm of its signaling. Reason: Downstream effector pathway, non-core relative to receptor activity. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0045121 membrane raft	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR partitions into membrane rafts/nanodomains that modulate its ligand binding and dimerization. Reason: Regulatory membrane subdomain; refinement of plasma-membrane localization, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0045739 positive regulation of DNA repair	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling can enhance DNA repair responses in some contexts. Reason: Downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0045740 positive regulation of DNA replication	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Mitogenic EGFR signaling promotes DNA replication during proliferation. Reason: Downstream proliferative effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling (and nuclear EGFR) promotes Pol II transcription of target genes. Reason: Downstream transcriptional output of signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0048471 perinuclear region of cytoplasm	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Endosomal and Golgi-associated EGFR accumulates in the perinuclear region during trafficking. Reason: Trafficking-derived localization, secondary to surface signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0050679 positive regulation of epithelial cell proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR drives proliferation of epithelial cells, central to epithelial development and homeostasis. Reason: Cell-type-specific proliferative effect downstream of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0050730 regulation of peptidyl-tyrosine phosphorylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR regulates tyrosine phosphorylation of substrates within its signaling network. Reason: Regulatory framing of its kinase activity at the network level; non-core relative to the direct catalytic term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0051015 actin filament binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR connects to the actin cytoskeleton during migration/ruffle formation, reported as actin filament binding. Reason: Real cytoskeletal association supporting migration, but downstream of core kinase signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR activation positively drives the PI3K-AKT survival pathway. Reason: Downstream regulatory effect of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0070141 response to UV-A	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: UV-A can transactivate EGFR (ligand-independent activation), linking it to UV stress responses. Reason: Stimulus-response role; transactivation context, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
GO:0070374 positive regulation of ERK1 and ERK2 cascade	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling activates the ERK1/2 (MAPK) cascade driving proliferative gene expression. Reason: Downstream effector cascade activation, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0071392 cellular response to estradiol stimulus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR participates in cellular responses to estradiol, partly via GPER1-dependent transactivation. Reason: Stimulus-response role, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
GO:0090037 positive regulation of protein kinase C signaling	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Via PLCgamma activation EGFR drives PKC signaling. Reason: Downstream effector arm, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0090263 positive regulation of canonical Wnt signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling can positively modulate canonical Wnt signaling via cross-talk. Reason: Pathway cross-talk effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0097489 multivesicular body, internal vesicle lumen	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR sorted for degradation is delivered into the internal vesicles of multivesicular bodies via the ESCRT machinery. Reason: Degradation-pathway localization downstream of activation, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0097708 intracellular vesicle	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR is found in intracellular vesicles of the endocytic/trafficking system after internalization. Reason: Generic trafficking compartment, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0098609 cell-cell adhesion	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR intersects cell-cell adhesion through cross-talk with junctional and adhesion molecules. Reason: Adhesion-related role downstream of/parallel to signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:1900087 positive regulation of G1/S transition of mitotic cell cycle	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR mitogenic signaling drives cell-cycle G1/S progression. Reason: Downstream proliferative effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:1902895 positive regulation of miRNA transcription	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling promotes transcription of specific miRNAs. Reason: Downstream transcriptional effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:1903078 positive regulation of protein localization to plasma membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling promotes recruitment/retention of partner proteins at the plasma membrane. Reason: Downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:1905208 negative regulation of cardiocyte differentiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling negatively regulates cardiomyocyte differentiation during heart development. Reason: Cardiac developmental role downstream of signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0005730 nucleolus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR has been reported in the nucleolus in specific contexts within its nuclear pool. Reason: Rare context-specific localization, secondary to canonical signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0018108 peptidyl-tyrosine phosphorylation	ISO GO_REF:0000096	ACCEPT	Summary: EGFR phosphorylates tyrosine residues on itself and on substrate proteins (e.g. EPS8, EPS15), the biochemical process of its kinase activity. Reason: Direct enzymatic process term matching the catalytic MF; retain as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0046777 protein autophosphorylation	ISO GO_REF:0000096	ACCEPT	Summary: Upon ligand-induced dimerization EGFR autophosphorylates C-terminal tail tyrosines (e.g. Y1092, Y1110, Y1172), creating docking sites for downstream adaptors. Reason: Defining direct catalytic output of the activated receptor, supported by IDA. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0097225 sperm midpiece	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR is detected in the sperm midpiece in spermatozoa. Reason: Tissue-specific localization, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0097228 sperm principal piece	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR is detected in the sperm flagellar principal piece. Reason: Tissue-specific localization, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0097229 sperm end piece	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR is detected in the sperm flagellar end piece, a tissue-specific localization. Reason: Cell-type-specific localization unrelated to core epithelial signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0004713 protein tyrosine kinase activity	ISO GO_REF:0000096	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005006 epidermal growth factor receptor activity	ISO GO_REF:0000096	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005102 signaling receptor binding	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: EGFR is itself the signaling receptor and engages receptor partners, but this term is too generic to describe its function. Reason: Non-informative binding term; receptor role captured by receptor-activity MF. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0005178 integrin binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR cross-talks with integrins, and integrin binding links it to adhesion-dependent signaling. Reason: Real adhesion-related interaction, secondary to core kinase signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:0005516 calmodulin binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR's juxtamembrane region binds calmodulin, a Ca2+-dependent modulator of receptor activity. Reason: Real regulatory interaction, but not the core MF of the receptor. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:0005768 endosome	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Activated EGFR is endocytosed into endosomes from which it can continue signaling before recycling or lysosomal degradation. Reason: Secondary localization arising from receptor trafficking, downstream of surface signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005829 cytosol	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR signaling and trafficking intermediates are detected in the cytosol. Reason: Generic secondary localization, not the primary functional site. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005929 cilium	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR has been reported at the cilium in some cell types. Reason: Context-specific localization, not core to receptor signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0006412 translation	ISO GO_REF:0000096	REMOVE	Summary: EGFR is a receptor tyrosine kinase with no role in the process of mRNA translation; this ISO-projected term is biologically implausible. Reason: No mechanistic basis; EGFR does not function in translation. Likely erroneous electronic projection. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0007173 epidermal growth factor receptor signaling pathway	ISO GO_REF:0000096	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007611 learning or memory	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR enhances learning and memory performance, a pleiotropic neural role. Reason: Behavioral/physiological role downstream of neural EGFR signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:0009986 cell surface	ISO GO_REF:0000096	ACCEPT	Summary: EGFR is displayed at the cell surface where it encounters extracellular EGF-family ligands. Reason: Primary surface localization supported by IDA; core. Retain over the REMOVE-tagged duplicate. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0016323 basolateral plasma membrane	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR localizes to the basolateral surface of polarized epithelia, consistent with its role in epithelial signaling. Reason: Polarity-specific subdomain of the primary localization, supported by IDA but non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0016324 apical plasma membrane	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: In polarized epithelia EGFR can localize to the apical plasma-membrane domain. Reason: Polarity-specific subdomain of its primary localization; non-core specialization. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0019901 protein kinase binding	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: EGFR contacts various protein kinases (e.g. SRC-family) but the generic 'protein kinase binding' term adds no specific functional detail. Reason: Non-informative binding parent; specific roles captured elsewhere. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0019903 protein phosphatase binding	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: EGFR is bound and dephosphorylated by phosphatases (PTPN1/2/6, PTPRJ/K), but the generic binding term does not specify this regulatory relationship. Reason: Uninformative MF term; the regulatory relationship is captured in process terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0030139 endocytic vesicle	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Ligand-activated EGFR is captured in endocytic vesicles during clathrin-mediated internalization. Reason: Trafficking-intermediate localization downstream of activation at the surface. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0032930 positive regulation of superoxide anion generation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR signaling can stimulate NADPH-oxidase-dependent superoxide generation. Reason: Downstream signaling effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0035556 intracellular signal transduction	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR initiates intracellular signal transduction cascades upon activation. Reason: Generic downstream process, non-core relative to the specific EGFR pathway. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0036064 ciliary basal body	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: EGFR is reported at the ciliary basal body in some contexts. Reason: Specialized localization, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0042311 vasodilation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR signaling participates in vascular vasodilation responses. Reason: Vascular physiological effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic and physiological evidence also implicates EGFR in bone/endochondral ossification and heart valve development.
GO:0042698 ovulation cycle	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR signaling participates in the ovulation cycle (cumulus expansion/ovulation). Reason: Reproductive physiology process downstream of signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic and physiological evidence also implicates EGFR in bone/endochondral ossification and heart valve development.
GO:0043066 negative regulation of apoptotic process	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR-PI3K-AKT signaling promotes cell survival by suppressing apoptosis, e.g. in keratinocytes. Reason: Pro-survival downstream effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0043410 positive regulation of MAPK cascade	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Phosphorylated EGFR recruits GRB2/SOS to activate the RAS-RAF-MEK-ERK MAPK cascade. Reason: Major downstream signaling output, but a regulatory effect downstream of the receptor's own activity. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0044877 protein-containing complex binding	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: EGFR associates with multiprotein complexes, but this generic binding term provides no specific functional information. Reason: Uninformative; complex membership is captured by receptor complex. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0045780 positive regulation of bone resorption	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR signaling promotes osteoclast-mediated bone resorption. Reason: Skeletal physiology effect downstream of signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic and physiological evidence also implicates EGFR in bone/endochondral ossification and heart valve development.
GO:0045907 positive regulation of vasoconstriction	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR transactivation (e.g. by GPCR agonists) contributes to vasoconstriction. Reason: Vascular physiological effect downstream of signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic and physiological evidence also implicates EGFR in bone/endochondral ossification and heart valve development.
GO:0045930 negative regulation of mitotic cell cycle	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: In some contexts EGFR signaling negatively regulates the mitotic cell cycle. Reason: Context-dependent downstream cell-cycle effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0048143 astrocyte activation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR signaling contributes to astrocyte activation in the CNS. Reason: Glial physiological role, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:0048408 epidermal growth factor binding	ISO GO_REF:0000096	ACCEPT	Summary: The EGFR extracellular L-domains directly bind EGF and other EGF-family ligands, the event that triggers receptor dimerization and activation. Reason: Core ligand-binding MF supported by IDA; central to receptor function. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0048661 positive regulation of smooth muscle cell proliferation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR signaling drives smooth muscle cell proliferation, e.g. in vascular remodeling. Reason: Cell-type-specific proliferative effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0048812 neuron projection morphogenesis	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR signaling shapes neuron projection morphogenesis. Reason: Neural developmental role, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:0051592 response to calcium ion	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR participates in cellular responses to calcium ion signaling. Reason: Stimulus-response role, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
GO:0051968 positive regulation of synaptic transmission, glutamatergic	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR positively modulates glutamatergic synaptic transmission. Reason: Neuronal physiological effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:0060252 positive regulation of glial cell proliferation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR promotes proliferation of glial cells in the CNS. Reason: Cell-type-specific proliferative effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0070257 positive regulation of mucus secretion	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR drives mucin/mucus secretion in epithelial (e.g. airway) tissue. Reason: Epithelial secretory effect downstream of signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic and physiological evidence also implicates EGFR in bone/endochondral ossification and heart valve development.
GO:0071364 cellular response to epidermal growth factor stimulus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: As the EGF receptor, EGFR mediates the cellular response to EGF stimulus. Reason: Response-to-stimulus framing of its core function; per principles, response-to-X terms are non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
GO:0097060 synaptic membrane	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR is found at synaptic membranes consistent with neuronal signaling roles in learning/memory. Reason: Neuron-specific localization downstream of EGFR's pleiotropic neural function. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:0097421 liver regeneration	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR mitogenic signaling drives hepatocyte proliferation during liver regeneration. Reason: Organ-level physiological process downstream of proliferative signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic and physiological evidence also implicates EGFR in bone/endochondral ossification and heart valve development.
GO:0098978 glutamatergic synapse	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR localizes to glutamatergic synapses where it modulates synaptic transmission. Reason: Neuron-specific localization, downstream pleiotropic role. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:1902722 positive regulation of prolactin secretion	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: EGFR signaling promotes prolactin secretion in endocrine contexts. Reason: Endocrine physiological effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic and physiological evidence also implicates EGFR in bone/endochondral ossification and heart valve development.
GO:0010467 gene expression	IMP PMID:28790147 Hepatocyte-Specific Deletion of EGFR in Mice Reduces Hepatic...	KEEP AS NON CORE	Summary: EGFR signaling alters gene expression programs controlling proliferation and survival. Reason: Very broad downstream process; non-core (and over-general), retained as pleiotropic effect. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0042908 xenobiotic transport	IMP PMID:28790147 Hepatocyte-Specific Deletion of EGFR in Mice Reduces Hepatic...	KEEP AS NON CORE	Summary: Altered xenobiotic transport in Egfr-perturbed cells is a distal phenotype (e.g. EGFR-dependent regulation of transporter expression), not a direct EGFR activity. Reason: Downstream phenotype of EGFR signaling; non-core (experimental IMP retained, not removed). Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0005515 protein binding	IPI PMID:22975324 Mig6 is a sensor of EGF receptor inactivation that directly ...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0005886 plasma membrane	IDA PMID:21946538 Epidermal growth factor receptor promotes glomerular injury ...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0004713 protein tyrosine kinase activity	ISO PMID:11894095 Cbl-CIN85-endophilin complex mediates ligand-induced downreg...	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway	ISO PMID:11894095 Cbl-CIN85-endophilin complex mediates ligand-induced downreg...	KEEP AS NON CORE	Summary: EGFR signaling is subject to feedback downregulation (CBL-mediated ubiquitination, endocytosis, LRIG1/ERRFI1/SOCS feedback inhibitors). Reason: Regulatory/feedback process on its own pathway, supported by IDA/IMP but non-core to the receptor's MF. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:0004713 protein tyrosine kinase activity	IDA PMID:15962011 Sprouty2 acts at the Cbl/CIN85 interface to inhibit epiderma...	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004713 protein tyrosine kinase activity	IMP PMID:11823423 A mutant EGF-receptor defective in ubiquitylation and endocy...	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004713 protein tyrosine kinase activity	IDA PMID:15383614 c-Cbl directs EGF receptors into an endocytic pathway that i...	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:11823423 A mutant EGF-receptor defective in ubiquitylation and endocy...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway	IMP PMID:11823423 A mutant EGF-receptor defective in ubiquitylation and endocy...	KEEP AS NON CORE	Summary: EGFR signaling is subject to feedback downregulation (CBL-mediated ubiquitination, endocytosis, LRIG1/ERRFI1/SOCS feedback inhibitors). Reason: Regulatory/feedback process on its own pathway, supported by IDA/IMP but non-core to the receptor's MF. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:0004713 protein tyrosine kinase activity	IMP PMID:15383614 c-Cbl directs EGF receptors into an endocytic pathway that i...	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004713 protein tyrosine kinase activity	IDA PMID:23457600 Berberine inhibits proliferation and down-regulates epiderma...	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:23457600 Berberine inhibits proliferation and down-regulates epiderma...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005886 plasma membrane	IDA PMID:15383614 c-Cbl directs EGF receptors into an endocytic pathway that i...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway	IDA PMID:23457600 Berberine inhibits proliferation and down-regulates epiderma...	KEEP AS NON CORE	Summary: EGFR signaling is subject to feedback downregulation (CBL-mediated ubiquitination, endocytosis, LRIG1/ERRFI1/SOCS feedback inhibitors). Reason: Regulatory/feedback process on its own pathway, supported by IDA/IMP but non-core to the receptor's MF. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
GO:0005886 plasma membrane	ISO PMID:15611079 Epigen, the last ligand of ErbB receptors, reveals intricate...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0004713 protein tyrosine kinase activity	ISO PMID:2472218 EGF induces tyrosine phosphorylation of phospholipase C-II: ...	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004713 protein tyrosine kinase activity	ISO PMID:9890893 Identification of tyrosine phosphorylation sites in human Ga...	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005006 epidermal growth factor receptor activity	ISO PMID:2176151 The tyrosine phosphorylated carboxyterminus of the EGF recep...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:9529375 Epidermal growth factor signaling and mitogenesis in Plcg1 n...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:12761849 EGF-stimulated signaling by means of PI3K, PLCgamma1, and PK...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007173 epidermal growth factor receptor signaling pathway	ISO PMID:9890893 Identification of tyrosine phosphorylation sites in human Ga...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:7678348 Expression of the epidermal growth factor receptor gene is r...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005886 plasma membrane	IDA PMID:6248866 Detection of epidermal growth factor-urogastrone and its rec...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0005886 plasma membrane	IDA PMID:7678348 Expression of the epidermal growth factor receptor gene is r...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0005886 plasma membrane	IDA PMID:8702723 The epidermal growth factor receptor couples transforming gr...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:7678348 Expression of the epidermal growth factor receptor gene is r...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IDA PMID:21897861 Betacellulin-induced beta cell proliferation and regeneratio...	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005886 plasma membrane	IDA PMID:21897861 Betacellulin-induced beta cell proliferation and regeneratio...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0038134 ERBB2-EGFR signaling pathway	IDA PMID:21897861 Betacellulin-induced beta cell proliferation and regeneratio...	ACCEPT	Summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling. Reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0005006 epidermal growth factor receptor activity	ISO PMID:11336639 Heterodimerization of the epidermal-growth-factor (EGF) rece...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005006 epidermal growth factor receptor activity	IMP PMID:18701712 Transactivation of EGF receptor and ErbB2 protects intestina...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005886 plasma membrane	ISO PMID:11336639 Heterodimerization of the epidermal-growth-factor (EGF) rece...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0038134 ERBB2-EGFR signaling pathway	ISO PMID:11336639 Heterodimerization of the epidermal-growth-factor (EGF) rece...	ACCEPT	Summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling. Reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0038134 ERBB2-EGFR signaling pathway	IMP PMID:18701712 Transactivation of EGF receptor and ErbB2 protects intestina...	ACCEPT	Summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling. Reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac...	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IDA PMID:8702723 The epidermal growth factor receptor couples transforming gr...	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:8702723 The epidermal growth factor receptor couples transforming gr...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0038134 ERBB2-EGFR signaling pathway	IDA PMID:8702723 The epidermal growth factor receptor couples transforming gr...	ACCEPT	Summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling. Reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IMP PMID:12399441 ErbB signaling regulates lineage determination of developing...	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IGI PMID:28783046 Epiregulin and EGFR interactions are involved in pain proces...	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IDA PMID:8456283 Betacellulin: a mitogen from pancreatic beta cell tumors.	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005886 plasma membrane	IGI PMID:28783046 Epiregulin and EGFR interactions are involved in pain proces...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0005886 plasma membrane	IDA PMID:8456283 Betacellulin: a mitogen from pancreatic beta cell tumors.	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0005886 plasma membrane	IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0007173 epidermal growth factor receptor signaling pathway	IMP PMID:12399441 ErbB signaling regulates lineage determination of developing...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007173 epidermal growth factor receptor signaling pathway	IGI PMID:28783046 Epiregulin and EGFR interactions are involved in pain proces...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:8456283 Betacellulin: a mitogen from pancreatic beta cell tumors.	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0038134 ERBB2-EGFR signaling pathway	IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac...	ACCEPT	Summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling. Reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IMP PMID:23333074 Amphiregulin enhances regulatory T cell-suppressive function...	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IMP PMID:23899604 Increased activation of the epidermal growth factor receptor...	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IMP PMID:30770250 A Macrophage-Pericyte Axis Directs Tissue Restoration via Am...	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0004714 transmembrane receptor protein tyrosine kinase activity	IDA PMID:7752576 Tyrosine kinase activity of the EGF receptor in murine metan...	ACCEPT	Summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity. Reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0005886 plasma membrane	IDA PMID:28494873 A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localiza...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0005886 plasma membrane	IDA PMID:7752576 Tyrosine kinase activity of the EGF receptor in murine metan...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0005886 plasma membrane	IDA PMID:8621573 STAT activation by epidermal growth factor (EGF) and amphire...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0007173 epidermal growth factor receptor signaling pathway	IMP PMID:23333074 Amphiregulin enhances regulatory T cell-suppressive function...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007173 epidermal growth factor receptor signaling pathway	IMP PMID:23899604 Increased activation of the epidermal growth factor receptor...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007173 epidermal growth factor receptor signaling pathway	IMP PMID:30770250 A Macrophage-Pericyte Axis Directs Tissue Restoration via Am...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:7752576 Tyrosine kinase activity of the EGF receptor in murine metan...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0005006 epidermal growth factor receptor activity	IGI PMID:16357442 Soluble form of heparin-binding EGF-like growth factor contr...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:21946538 Epidermal growth factor receptor promotes glomerular injury ...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0038134 ERBB2-EGFR signaling pathway	IDA PMID:21946538 Epidermal growth factor receptor promotes glomerular injury ...	ACCEPT	Summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling. Reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:6248866 Detection of epidermal growth factor-urogastrone and its rec...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:7752576 Tyrosine kinase activity of the EGF receptor in murine metan...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:6248866 Detection of epidermal growth factor-urogastrone and its rec...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0005515 protein binding	IPI PMID:15695332 Suppressor of cytokine signaling (SOCS)-5 is a potential neg...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0005515 protein binding	IPI PMID:15728722 Local phosphatidylinositol 3,4,5-trisphosphate accumulation ...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:1902966 positive regulation of protein localization to early endosome	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: EGFR activation drives recruitment of sorting machinery to early endosomes during its trafficking. Reason: Trafficking-associated regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:11940581 Protein kinase C-alpha and protein kinase C-epsilon are requ...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0071363 cellular response to growth factor stimulus	IDA PMID:8702723 The epidermal growth factor receptor couples transforming gr...	KEEP AS NON CORE	Summary: EGFR mediates cellular responses to EGF-family growth factor stimuli. Reason: Broad response-to-stimulus term, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
GO:0030307 positive regulation of cell growth	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: EGFR signaling promotes cell growth (mass increase) in responsive cells. Reason: Downstream growth effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0048408 epidermal growth factor binding	IDA PMID:7678348 Expression of the epidermal growth factor receptor gene is r...	ACCEPT	Summary: The EGFR extracellular L-domains directly bind EGF and other EGF-family ligands, the event that triggers receptor dimerization and activation. Reason: Core ligand-binding MF supported by IDA; central to receptor function. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0005515 protein binding	IPI PMID:15467833 CEACAM1 modulates epidermal growth factor receptor--mediated...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0001942 hair follicle development	IGI PMID:9030684 Mutation in Sos1 dominantly enhances a weak allele of the EG...	KEEP AS NON CORE	Summary: EGFR signaling is required for normal hair follicle development (e.g. waved-2 phenotype). Reason: Tissue-development role downstream of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0061029 eyelid development in camera-type eye	IGI PMID:9030684 Mutation in Sos1 dominantly enhances a weak allele of the EG...	KEEP AS NON CORE	Summary: EGFR signaling is required for eyelid morphogenesis (open-eyelid phenotypes in pathway mutants). Reason: Organ-development role downstream of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0005515 protein binding	IPI PMID:25744720 Lung Tumor Suppressor GPRC5A Binds EGFR and Restrains Its Ef...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0009986 cell surface	IDA PMID:23918928 Furin is the primary in vivo convertase of angiopoietin-like...	ACCEPT	Summary: EGFR is displayed at the cell surface where it encounters extracellular EGF-family ligands. Reason: Primary surface localization supported by IDA; core. Retain over the REMOVE-tagged duplicate. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0043235 receptor complex	ISO PMID:23382219 Structural basis for endosomal trafficking of diverse transm...	ACCEPT	Summary: Active EGFR exists as a ligand-induced homo- or heterodimeric receptor complex (e.g. with ERBB2), the signaling-competent unit. Reason: Captures the functional dimeric receptor assembly; core CC supported by IBA/ISO. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0071230 cellular response to amino acid stimulus	IDA PMID:22711986 Calpain 2 activated through N-methyl-D-aspartic acid recepto...	KEEP AS NON CORE	Summary: EGFR mediates cellular responses to amino acid stimulus in nutrient signaling contexts. Reason: Stimulus-response role, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
GO:0001934 positive regulation of protein phosphorylation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Active EGFR promotes phosphorylation of effector proteins in its signaling network. Reason: Broad downstream regulatory effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0003682 chromatin binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Nuclear EGFR has been reported to bind chromatin and act as a transcriptional co-regulator in specific contexts. Reason: Non-canonical activity of the nuclear pool, downstream of canonical signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause thin medulla, polyuria, and impaired urine concentrating ability.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: EGFR signaling (and nuclear EGFR) promotes Pol II transcription of target genes. Reason: Downstream transcriptional output of signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0070374 positive regulation of ERK1 and ERK2 cascade	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: EGFR signaling activates the ERK1/2 (MAPK) cascade driving proliferative gene expression. Reason: Downstream effector cascade activation, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0071392 cellular response to estradiol stimulus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: EGFR participates in cellular responses to estradiol, partly via GPER1-dependent transactivation. Reason: Stimulus-response role, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
GO:0005515 protein binding	IPI PMID:17726113 Inhibition of the leucine-rich repeat protein LINGO-1 enhanc...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0005634 nucleus	IDA PMID:20208556 Presenilin modulates EGFR signaling and cell transformation ...	KEEP AS NON CORE	Summary: A pool of EGFR translocates to the nucleus (via Golgi/ER, aided by PIKFYVE) where it can influence transcription in specific contexts. Reason: Context-specific non-canonical localization, secondary to membrane signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0048146 positive regulation of fibroblast proliferation	IMP PMID:20208556 Presenilin modulates EGFR signaling and cell transformation ...	KEEP AS NON CORE	Summary: EGFR signaling stimulates fibroblast proliferation. Reason: Cell-type-specific proliferative effect, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0048471 perinuclear region of cytoplasm	IDA PMID:20208556 Presenilin modulates EGFR signaling and cell transformation ...	KEEP AS NON CORE	Summary: Endosomal and Golgi-associated EGFR accumulates in the perinuclear region during trafficking. Reason: Trafficking-derived localization, secondary to surface signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0005768 endosome	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Activated EGFR is endocytosed into endosomes from which it can continue signaling before recycling or lysosomal degradation. Reason: Secondary localization arising from receptor trafficking, downstream of surface signaling. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.
GO:0004888 transmembrane signaling receptor activity	ISO GO_REF:0000008	MODIFY	Summary: EGFR is a transmembrane signaling receptor, but more precisely a receptor tyrosine kinase that couples ligand binding to intrinsic catalytic activity. Reason: Correct but too general a receptor MF; replace with the kinase-coupled RTK term capturing the catalytic mechanism. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0007166 cell surface receptor signaling pathway	ISO GO_REF:0000008	KEEP AS NON CORE	Summary: EGFR signals via a cell-surface receptor signaling pathway; the EGFR-specific term captures the precise function. Reason: Over-general parent of the specific EGFR pathway; keep as non-core rather than removing. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007173 epidermal growth factor receptor signaling pathway	ISO GO_REF:0000008	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0008284 positive regulation of cell population proliferation	ISO GO_REF:0000008	KEEP AS NON CORE	Summary: EGFR is a mitogenic receptor driving proliferation of many cell types. Reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0005515 protein binding	IPI PMID:16120644 Regulation of epidermal growth factor receptor down-regulati...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0004713 protein tyrosine kinase activity	ISS GO_REF:0000024	ACCEPT	Summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail. Reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0001892 embryonic placenta development	IMP PMID:7618084 Targeted disruption of mouse EGF receptor: effect of genetic...	KEEP AS NON CORE	Summary: EGFR is essential for placental development; embryonic lethality in Egfr-null mice is due to placental defects. Reason: Developmental role downstream of receptor signaling, non-core but biologically important. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0001942 hair follicle development	IMP PMID:7618084 Targeted disruption of mouse EGF receptor: effect of genetic...	KEEP AS NON CORE	Summary: EGFR signaling is required for normal hair follicle development (e.g. waved-2 phenotype). Reason: Tissue-development role downstream of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0008544 epidermis development	IMP PMID:7618084 Targeted disruption of mouse EGF receptor: effect of genetic...	KEEP AS NON CORE	Summary: EGFR is required for epidermal development; loss causes skin barrier defects and dermatitis. Reason: Organ-development role downstream of EGFR's proliferative/survival signaling; pleiotropic, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0021795 cerebral cortex cell migration	IMP PMID:7618084 Targeted disruption of mouse EGF receptor: effect of genetic...	KEEP AS NON CORE	Summary: EGFR signaling influences migration of cells in the developing cerebral cortex. Reason: Developmental neuronal migration role, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0048546 digestive tract morphogenesis	IMP PMID:7618084 Targeted disruption of mouse EGF receptor: effect of genetic...	KEEP AS NON CORE	Summary: EGFR is required for normal gastrointestinal tract morphogenesis; Egfr-null mice show gut defects. Reason: Organ-development role downstream of epithelial signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0050679 positive regulation of epithelial cell proliferation	IMP PMID:7618084 Targeted disruption of mouse EGF receptor: effect of genetic...	KEEP AS NON CORE	Summary: EGFR drives proliferation of epithelial cells, central to epithelial development and homeostasis. Reason: Cell-type-specific proliferative effect downstream of receptor signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0060571 morphogenesis of an epithelial fold	IMP PMID:7618084 Targeted disruption of mouse EGF receptor: effect of genetic...	KEEP AS NON CORE	Summary: EGFR-driven epithelial proliferation contributes to morphogenesis of epithelial folds. Reason: Morphogenetic role downstream of epithelial signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0000902 cell morphogenesis	IGI PMID:17686994 The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskel...	KEEP AS NON CORE	Summary: EGFR signaling influences cell shape/morphogenesis during development. Reason: Broad developmental morphogenesis effect, non-core; not contradicted, so retain rather than REMOVE. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0007173 epidermal growth factor receptor signaling pathway	IMP PMID:17686994 The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskel...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0007435 salivary gland morphogenesis	IMP PMID:10521784 Submandibular gland morphogenesis: stage-specific expression...	KEEP AS NON CORE	Summary: EGFR is required for branching morphogenesis of the salivary gland. Reason: Organ-morphogenesis role downstream of epithelial EGFR signaling, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Mouse genetic evidence supports EGFR as an essential regulator of epithelial organ development and postnatal epithelial homeostasis.
GO:0042127 regulation of cell population proliferation	IGI PMID:11818567 Importance of epidermal growth factor receptor signaling in ...	KEEP AS NON CORE	Summary: EGFR regulates proliferation of target cell populations. Reason: Broad regulatory proliferation term, non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0008284 positive regulation of cell population proliferation	IGI PMID:18656477 Betacellulin stimulates growth of the mouse intestinal epith...	KEEP AS NON CORE	Summary: EGFR is a mitogenic receptor driving proliferation of many cell types. Reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0005886 plasma membrane	IDA PMID:7641815 Altering the expression of cell surface beta 1,4-galactosylt...	ACCEPT	Summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation. Reason: Primary, defining localization supported by IDA/IBA/IGI; core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0007173 epidermal growth factor receptor signaling pathway	IGI PMID:7641815 Altering the expression of cell surface beta 1,4-galactosylt...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0008284 positive regulation of cell population proliferation	IGI PMID:7641815 Altering the expression of cell surface beta 1,4-galactosylt...	KEEP AS NON CORE	Summary: EGFR is a mitogenic receptor driving proliferation of many cell types. Reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0046777 protein autophosphorylation	IDA PMID:15314156 MUC20 suppresses the hepatocyte growth factor-induced Grb2-R...	ACCEPT	Summary: Upon ligand-induced dimerization EGFR autophosphorylates C-terminal tail tyrosines (e.g. Y1092, Y1110, Y1172), creating docking sites for downstream adaptors. Reason: Defining direct catalytic output of the activated receptor, supported by IDA. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:15695332 Suppressor of cytokine signaling (SOCS)-5 is a potential neg...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0005006 epidermal growth factor receptor activity	IDA PMID:14712229 G-protein-coupled receptor-mediated activation of rap GTPase...	ACCEPT	Summary: EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene. Reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Egfr encodes EGFR, the prototypical member of the ErbB family of receptor tyrosine kinases.
GO:0007173 epidermal growth factor receptor signaling pathway	IDA PMID:14712229 G-protein-coupled receptor-mediated activation of rap GTPase...	ACCEPT	Summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling. Reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:14712229 G-protein-coupled receptor-mediated activation of rap GTPase...	KEEP AS NON CORE	Summary: EGFR is a mitogenic receptor driving proliferation of many cell types. Reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md In mouse skin, EGFR supports keratinocyte survival, proliferation, migration, and wound healing, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
GO:0005515 protein binding	IPI PMID:12919676 CAML is required for efficient EGF receptor recycling.	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0016323 basolateral plasma membrane	IDA PMID:7723235 Epidermal growth factor receptor expression is abnormal in m...	KEEP AS NON CORE	Summary: EGFR localizes to the basolateral surface of polarized epithelia, consistent with its role in epithelial signaling. Reason: Polarity-specific subdomain of the primary localization, supported by IDA but non-core. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is primarily a plasma-membrane receptor that is dynamically redistributed to endosomes after activation and has been reported to access nuclear and mitochondrial pools in some contexts.
GO:0016301 kinase activity	IDA PMID:12808090 Gab1 is an integrator of cell death versus cell survival sig...	MODIFY	Summary: EGFR has kinase activity, but the unqualified term loses the tyrosine/receptor specificity that defines EGFR. Reason: Over-general parent of the catalytic MF; replace with transmembrane receptor protein tyrosine kinase activity. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is a protein-tyrosine kinase whose core catalytic function is to transfer the γ-phosphate from ATP to tyrosine residues on protein substrates.
GO:0007165 signal transduction	IDA PMID:11940581 Protein kinase C-alpha and protein kinase C-epsilon are requ...	MARK AS OVER ANNOTATED	Summary: EGFR is a signal transducer, but this top-level process term is uninformative when the specific EGFR signaling pathway is annotated. Reason: Over-general process parent; specific EGFR signaling pathway captured separately. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0050730 regulation of peptidyl-tyrosine phosphorylation	IMP PMID:11940581 Protein kinase C-alpha and protein kinase C-epsilon are requ...	KEEP AS NON CORE	Summary: EGFR regulates tyrosine phosphorylation of substrates within its signaling network. Reason: Regulatory framing of its kinase activity at the network level; non-core relative to the direct catalytic term. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an asymmetric kinase dimer) that drives autophosphorylation of the C-terminal tail.
GO:0005515 protein binding	IPI PMID:11274221 Src and Pyk2 mediate G-protein-coupled receptor activation o...	MARK AS OVER ANNOTATED	Summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function. Reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
GO:0030139 endocytic vesicle	IDA PMID:10534613 Ectodysplasin, a protein required for epithelial morphogenes...	KEEP AS NON CORE	Summary: Ligand-activated EGFR is captured in endocytic vesicles during clathrin-mediated internalization. Reason: Trafficking-intermediate localization downstream of activation at the surface. Supporting Evidence: UniProt:Q01279 FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand. file:mouse/Egfr/Egfr-deep-research-falcon.md EGFR is internalized via clathrin-mediated endocytosis as well as non-clathrin (e.g., caveolar) routes.

Aspect	Key points	Best supporting sources
Identity/domains	• UniProt Q01279 = mouse Egfr/EGFR (ErbB1), a single-pass receptor tyrosine kinase • Extracellular ligand-binding region, transmembrane helix, juxtamembrane segment, intracellular Tyr kinase domain, C-terminal tail • Reported localization includes plasma membrane, endosomes, and context-dependent nuclear/mitochondrial pools	(huang2021illuminatingunderstudiedkinases pages 104-105, chen2016expressionandfunction pages 4-5, chen2016expressionandfunction media 2b0434df)
Enzymatic activity	• Intrinsic protein-tyrosine kinase activated by ligand-induced dimerization/asymmetric kinase dimer formation • Autophosphorylates C-terminal tyrosines to create docking sites for adaptors/effectors • Activity is modulated by juxtamembrane interactions and regulatory phosphorylation (e.g., human S768/mouse-aligned S770 context)	(chen2016expressionandfunction pages 4-5, huang2021illuminatingunderstudiedkinases pages 105-109, kozlova2024celladhesionmolecules pages 4-6)
Key autophosphorylation sites	• Major EGFR phosphotyrosines highlighted in authoritative review: Y992, Y1068, Y1086, Y1148, Y1173 • Src can also phosphorylate Y845 • These phosphosites recruit signaling proteins rather than serving as catalytic residues per se	(chen2016expressionandfunction pages 4-5, chen2016expressionandfunction media 2b0434df)
Major pathways	• Canonical outputs: RAS–RAF–MEK–ERK, PI3K–AKT, STAT1/STAT3 • Additional receptor-proximal signaling includes Shc/Grb2/SOS1, Gab1/SHP2, PLCγ-linked lipid remodeling • Ligand identity and trafficking route can bias duration/intensity of outputs	(chen2016expressionandfunction pages 4-5, zhou2024newdirectionsfor pages 1-2, chen2016expressionandfunction media 2b0434df)
Localization/trafficking	• Surface EGFR is internalized by clathrin-dependent and non-clathrin routes, then sorted to recycling or lysosomal degradation • Internalized EGFR can continue signaling from early endosomes; ubiquitination/Cbl proteins and ESCRT machinery control downregulation • Nuclear EGFR is documented in some contexts, though plasma membrane/endosomes are the primary functional sites	(chen2016expressionandfunction pages 4-5, pinillamacua2023cblandcblb pages 13-13, kozlova2024celladhesionmolecules pages 4-6, lin2023endosomalarl4aattenuates pages 1-2)
Mouse genetics/physiology	• Mouse loss-of-function models show essential roles in epidermis/hair, lung branching and alveolization, kidney collecting duct physiology, bone and heart valve development • Keratinocyte or epidermal EGFR loss causes barrier defects/inflammation; collecting-duct deletion impairs urine concentration • Gut and other epithelial phenotypes support a core role in epithelial proliferation, survival, repair	(chen2016expressionandfunction pages 7-8, wong2003transgenicandknockout pages 2-4, chen2016expressionandfunction pages 8-9)
Recent (2023-2024) mechanistic advances	• Tetraspanin nanodomains gate ligand binding; unliganded EGFR confinement favors EGF binding, then ligand-bound receptor shifts toward clathrin/oligomer confinement • PIP2 nanodomains promote EGFR dimerization, autophosphorylation, and EGFR/EphA2 complex formation • New work shows ligand-free kinase-active oligomers in resistant EGFR mutants and autophagic clearance of hypersignaling endosomes	(abe2024bilateralregulationof pages 1-2, sugiyama2023confinementofunliganded pages 8-9, singh2024phosphatidylinositol45bisphosphatedrives pages 1-2, iyer2024drugresistantegfrmutations pages 1-2, sugiyama2023confinementofunliganded pages 14-15)
Applications/statistics	• EGFR biology underpins approved antibodies/TKIs and organoid-based resistance modeling; CRC organoids are used as preclinical anti-EGFR testbeds • 2024 review lists 8 FDA-approved EGFR/ErbB-targeting drugs over two decades; first/second-generation TKI resistance often emerges in ~8–14 months • PET/CT radiomics meta-analysis for EGFR mutation prediction in NSCLC reported AUC 0.84 training and 0.82 validation across 3,763 patients	(tardito2024epidermalgrowthfactor pages 1-2, hawash2024advancesincancer pages 21-23, ma2024predictivevalueof pages 2-3)

📄 View Raw YAML

id: Q01279
gene_symbol: Egfr
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: Epidermal growth factor receptor is a single-pass receptor tyrosine kinase for EGF-family ligands. Ligand-induced dimerization activates receptor autophosphorylation and docking of signaling adaptors, coupling the plasma membrane receptor to RAS-MAPK, PI3K-AKT, PLC-gamma/PKC, STAT, endocytic trafficking, proliferation, differentiation, and survival outputs.
existing_annotations:
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0043235
    label: receptor complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Active EGFR exists as a ligand-induced homo- or heterodimeric receptor complex (e.g. with ERBB2), the signaling-competent unit.
    action: ACCEPT
    reason: Captures the functional dimeric receptor assembly; core CC supported by IBA/ISO.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0030182
    label: neuron differentiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: EGFR contributes to neuronal differentiation in the nervous system.
    action: KEEP_AS_NON_CORE
    reason: Developmental role downstream of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: EGFR-PI3K-AKT signaling promotes cell survival by suppressing apoptosis, e.g. in keratinocytes.
    action: KEEP_AS_NON_CORE
    reason: Pro-survival downstream effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Phosphorylated EGFR recruits GRB2/SOS to activate the RAS-RAF-MEK-ERK MAPK cascade.
    action: KEEP_AS_NON_CORE
    reason: Major downstream signaling output, but a regulatory effect downstream of the receptor's own activity.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: EGFR drives proliferation of epithelial cells, central to epithelial development and homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific proliferative effect downstream of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0009925
    label: basal plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: In polarized epithelial cells EGFR is found at the basal plasma-membrane domain.
    action: KEEP_AS_NON_CORE
    reason: Polarity-specific subdomain; non-core specialization of plasma membrane.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0048408
    label: epidermal growth factor binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: The EGFR extracellular L-domains directly bind EGF and other EGF-family ligands, the event that triggers receptor dimerization and activation.
    action: ACCEPT
    reason: Core ligand-binding MF supported by IDA; central to receptor function.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: As a single-pass membrane protein EGFR is found on Golgi membranes during transit.
    action: KEEP_AS_NON_CORE
    reason: Secretory-pathway localization, secondary to surface signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: EGFR is a protein kinase, but specifically a transmembrane receptor tyrosine kinase; the bare parent term is uninformative for this receptor.
    action: MODIFY
    reason: Generic parent for a receptor tyrosine kinase; replace with the specific RTK MF term.
    proposed_replacement_terms:
    - id: GO:0004714
      label: transmembrane receptor protein tyrosine kinase activity
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: EGFR's kinase domain binds ATP (residues 720-728, 747, 792-793, 857) as the phosphate donor for tyrosine phosphorylation.
    action: ACCEPT
    reason: Required cofactor binding for the catalytic MF; correct and core despite IEA evidence.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: A pool of EGFR translocates to the nucleus (via Golgi/ER, aided by PIKFYVE) where it can influence transcription in specific contexts.
    action: KEEP_AS_NON_CORE
    reason: Context-specific non-canonical localization, secondary to membrane signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Activated EGFR is endocytosed into endosomes from which it can continue signaling before recycling or lysosomal degradation.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization arising from receptor trafficking, downstream of surface signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Nascent EGFR transits the ER membrane during biosynthesis, and retrograde Golgi-to-ER transport routes a nuclear pool.
    action: KEEP_AS_NON_CORE
    reason: Biosynthetic/retrograde compartment, secondary to the receptor's signaling role.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0007169
    label: cell surface receptor protein tyrosine kinase signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: EGFR signals as a cell-surface receptor tyrosine kinase, but for this gene the specific EGFR signaling pathway term is the precise descriptor.
    action: MODIFY
    reason: Correct but generic parent pathway; replace with the EGFR-specific signaling pathway term.
    proposed_replacement_terms:
    - id: GO:0007173
      label: epidermal growth factor receptor signaling pathway
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Internalized EGFR associates with endosomal membranes during its post-activation trafficking and downregulation.
    action: KEEP_AS_NON_CORE
    reason: Secondary trafficking-derived localization, not the primary functional site.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: EGFR is a membrane protein, but the unqualified 'membrane' CC is uninformative when its plasma-membrane localization is established.
    action: MODIFY
    reason: Over-general CC parent; replace with plasma membrane.
    proposed_replacement_terms: &id001
    - id: GO:0005886
      label: plasma membrane
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0021537
    label: telencephalon development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: EGFR contributes to telencephalon (forebrain) development.
    action: KEEP_AS_NON_CORE
    reason: Developmental role downstream of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0030139
    label: endocytic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Ligand-activated EGFR is captured in endocytic vesicles during clathrin-mediated internalization.
    action: KEEP_AS_NON_CORE
    reason: Trafficking-intermediate localization downstream of activation at the surface.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Nuclear-translocated EGFR is associated with the nuclear membrane as a single-pass membrane protein.
    action: KEEP_AS_NON_CORE
    reason: Specialized non-canonical localization, not core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0042059
    label: negative regulation of epidermal growth factor receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: EGFR signaling is subject to feedback downregulation (CBL-mediated ubiquitination, endocytosis, LRIG1/ERRFI1/SOCS feedback inhibitors).
    action: KEEP_AS_NON_CORE
    reason: Regulatory/feedback process on its own pathway, supported by IDA/IMP but non-core to the receptor's MF.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16954185
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21439278
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22975374
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23799367
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Nuclear EGFR has been reported to bind chromatin and act as a transcriptional co-regulator in specific contexts.
    action: KEEP_AS_NON_CORE
    reason: Non-canonical activity of the nuclear pool, downstream of canonical signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:0004888
    label: transmembrane signaling receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR is a transmembrane signaling receptor, but more precisely a receptor tyrosine kinase that couples ligand binding to intrinsic catalytic activity.
    action: MODIFY
    reason: Correct but too general a receptor MF; replace with the kinase-coupled RTK term capturing the catalytic mechanism.
    proposed_replacement_terms: &id003
    - id: GO:0004714
      label: transmembrane receptor protein tyrosine kinase activity
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Internalized/trafficking EGFR and its cytoplasmic kinase domain are detected in the cytoplasmic compartment.
    action: KEEP_AS_NON_CORE
    reason: Broad secondary localization, downstream of membrane localization.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR passes through the Golgi during maturation and in retrograde trafficking toward the nucleus.
    action: KEEP_AS_NON_CORE
    reason: Biosynthetic/secretory pathway compartment, not the primary functional site.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR is a signal transducer, but this top-level process term is uninformative when the specific EGFR signaling pathway is annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-general process parent; specific EGFR signaling pathway captured separately.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: EGFR is displayed at the cell surface where it encounters extracellular EGF-family ligands.
    action: ACCEPT
    reason: Primary surface localization supported by IDA; core. Retain over the REMOVE-tagged duplicate.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: EGFR localizes to the basolateral surface of polarized epithelia, consistent with its role in epithelial signaling.
    action: KEEP_AS_NON_CORE
    reason: Polarity-specific subdomain of the primary localization, supported by IDA but non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR binds numerous enzymes (kinases, phosphatases, ligases), but 'enzyme binding' is a generic catch-all conveying no specific function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative parent binding term; specific enzyme interactions captured elsewhere.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR interacts with kinases within signaling complexes, but 'kinase binding' is a generic uninformative term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative binding term, redundant with protein kinase binding.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0019903
    label: protein phosphatase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR is bound and dephosphorylated by phosphatases (PTPN1/2/6, PTPRJ/K), but the generic binding term does not specify this regulatory relationship.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; the regulatory relationship is captured in process terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0030054
    label: cell junction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR is detected at epithelial cell junctions where it intersects adhesion signaling.
    action: KEEP_AS_NON_CORE
    reason: Specialized localization linked to adhesion, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0030296
    label: protein tyrosine kinase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR's intrinsic activity is that of a tyrosine kinase, not an activator of another tyrosine kinase; the IEA term mis-types its function.
    action: MODIFY
    reason: Activator-activity framing is wrong-essence for the receptor itself; replace with its true RTK MF term.
    proposed_replacement_terms:
    - id: GO:0004714
      label: transmembrane receptor protein tyrosine kinase activity
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling promotes cell growth (mass increase) in responsive cells.
    action: KEEP_AS_NON_CORE
    reason: Downstream growth effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR (via CCDC88A/GIV and cytoskeletal remodeling) promotes cell migration, important in wound healing.
    action: KEEP_AS_NON_CORE
    reason: Downstream motility effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Activated EGFR binds CBL/CBLB and other E3 ligases (RNF115, RNF126) that ubiquitinate it for endosomal sorting and degradation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction central to receptor downregulation, but a regulatory partner binding rather than the core MF.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:0031901
    label: early endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: After ligand-induced internalization EGFR resides on early endosome membranes, where sorting decisions (recycle vs degrade) shape signal duration.
    action: KEEP_AS_NON_CORE
    reason: Real post-activation trafficking compartment downstream of plasma-membrane signaling; not the primary site.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0032587
    label: ruffle membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Activated EGFR localizes to membrane ruffles during EGF-stimulated cytoskeletal remodeling and migration.
    action: KEEP_AS_NON_CORE
    reason: Migration-associated membrane subdomain, secondary to signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR is part of signaling complexes, but the bare 'protein-containing complex' CC term is too generic; the receptor complex term is appropriate.
    action: MODIFY
    reason: Over-general cellular component; replace with receptor complex.
    proposed_replacement_terms: &id002
    - id: GO:0043235
      label: receptor complex
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0034165
    label: positive regulation of toll-like receptor 9 signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR can positively regulate TLR9 signaling in immune/inflammatory contexts.
    action: KEEP_AS_NON_CORE
    reason: Pathway cross-talk effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling.
    action: ACCEPT
    reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0042177
    label: negative regulation of protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling can stabilize partner proteins, negatively regulating their catabolism.
    action: KEEP_AS_NON_CORE
    reason: Indirect downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0042327
    label: positive regulation of phosphorylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling increases phosphorylation of numerous downstream substrates.
    action: KEEP_AS_NON_CORE
    reason: Broad downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR homodimerizes, but the generic 'identical protein binding' term does not capture the receptor-dimerization mechanism meaningfully.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic term; dimerization is better captured by receptor complex/receptor-activity terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR-PI3K-AKT signaling promotes cell survival by suppressing apoptosis, e.g. in keratinocytes.
    action: KEEP_AS_NON_CORE
    reason: Pro-survival downstream effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0043235
    label: receptor complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Active EGFR exists as a ligand-induced homo- or heterodimeric receptor complex (e.g. with ERBB2), the signaling-competent unit.
    action: ACCEPT
    reason: Captures the functional dimeric receptor assembly; core CC supported by IBA/ISO.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Phosphorylated EGFR recruits GRB2/SOS to activate the RAS-RAF-MEK-ERK MAPK cascade.
    action: KEEP_AS_NON_CORE
    reason: Major downstream signaling output, but a regulatory effect downstream of the receptor's own activity.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR engages PI3K to activate AKT, a major pro-survival arm of its signaling.
    action: KEEP_AS_NON_CORE
    reason: Downstream effector pathway, non-core relative to receptor activity.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR partitions into membrane rafts/nanodomains that modulate its ligand binding and dimerization.
    action: KEEP_AS_NON_CORE
    reason: Regulatory membrane subdomain; refinement of plasma-membrane localization, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0045739
    label: positive regulation of DNA repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling can enhance DNA repair responses in some contexts.
    action: KEEP_AS_NON_CORE
    reason: Downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0045740
    label: positive regulation of DNA replication
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Mitogenic EGFR signaling promotes DNA replication during proliferation.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling (and nuclear EGFR) promotes Pol II transcription of target genes.
    action: KEEP_AS_NON_CORE
    reason: Downstream transcriptional output of signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Endosomal and Golgi-associated EGFR accumulates in the perinuclear region during trafficking.
    action: KEEP_AS_NON_CORE
    reason: Trafficking-derived localization, secondary to surface signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: EGFR drives proliferation of epithelial cells, central to epithelial development and homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific proliferative effect downstream of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0051015
    label: actin filament binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR connects to the actin cytoskeleton during migration/ruffle formation, reported as actin filament binding.
    action: KEEP_AS_NON_CORE
    reason: Real cytoskeletal association supporting migration, but downstream of core kinase signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR activation positively drives the PI3K-AKT survival pathway.
    action: KEEP_AS_NON_CORE
    reason: Downstream regulatory effect of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0070141
    label: response to UV-A
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: UV-A can transactivate EGFR (ligand-independent activation), linking it to UV stress responses.
    action: KEEP_AS_NON_CORE
    reason: Stimulus-response role; transactivation context, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling activates the ERK1/2 (MAPK) cascade driving proliferative gene expression.
    action: KEEP_AS_NON_CORE
    reason: Downstream effector cascade activation, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0071392
    label: cellular response to estradiol stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR participates in cellular responses to estradiol, partly via GPER1-dependent transactivation.
    action: KEEP_AS_NON_CORE
    reason: Stimulus-response role, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
- term:
    id: GO:0090037
    label: positive regulation of protein kinase C signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Via PLCgamma activation EGFR drives PKC signaling.
    action: KEEP_AS_NON_CORE
    reason: Downstream effector arm, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling can positively modulate canonical Wnt signaling via cross-talk.
    action: KEEP_AS_NON_CORE
    reason: Pathway cross-talk effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0097489
    label: multivesicular body, internal vesicle lumen
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR sorted for degradation is delivered into the internal vesicles of multivesicular bodies via the ESCRT machinery.
    action: KEEP_AS_NON_CORE
    reason: Degradation-pathway localization downstream of activation, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0097708
    label: intracellular vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR is found in intracellular vesicles of the endocytic/trafficking system after internalization.
    action: KEEP_AS_NON_CORE
    reason: Generic trafficking compartment, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0098609
    label: cell-cell adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR intersects cell-cell adhesion through cross-talk with junctional and adhesion molecules.
    action: KEEP_AS_NON_CORE
    reason: Adhesion-related role downstream of/parallel to signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:1902895
    label: positive regulation of miRNA transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling promotes transcription of specific miRNAs.
    action: KEEP_AS_NON_CORE
    reason: Downstream transcriptional effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:1903078
    label: positive regulation of protein localization to plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling promotes recruitment/retention of partner proteins at the plasma membrane.
    action: KEEP_AS_NON_CORE
    reason: Downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:1905208
    label: negative regulation of cardiocyte differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGFR signaling negatively regulates cardiomyocyte differentiation during heart development.
    action: KEEP_AS_NON_CORE
    reason: Cardiac developmental role downstream of signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0001934
    label: positive regulation of protein phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Active EGFR promotes phosphorylation of effector proteins in its signaling network.
    action: KEEP_AS_NON_CORE
    reason: Broad downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Nuclear EGFR has been reported to bind chromatin and act as a transcriptional co-regulator in specific contexts.
    action: KEEP_AS_NON_CORE
    reason: Non-canonical activity of the nuclear pool, downstream of canonical signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: contributes_to
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: A pool of EGFR translocates to the nucleus (via Golgi/ER, aided by PIKFYVE) where it can influence transcription in specific contexts.
    action: KEEP_AS_NON_CORE
    reason: Context-specific non-canonical localization, secondary to membrane signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Internalized/trafficking EGFR and its cytoplasmic kinase domain are detected in the cytoplasmic compartment.
    action: KEEP_AS_NON_CORE
    reason: Broad secondary localization, downstream of membrane localization.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Activated EGFR is endocytosed into endosomes from which it can continue signaling before recycling or lysosomal degradation.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization arising from receptor trafficking, downstream of surface signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR passes through the Golgi during maturation and in retrograde trafficking toward the nucleus.
    action: KEEP_AS_NON_CORE
    reason: Biosynthetic/secretory pathway compartment, not the primary functional site.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is a signal transducer, but this top-level process term is uninformative when the specific EGFR signaling pathway is annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-general process parent; specific EGFR signaling pathway captured separately.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is a mitogenic receptor driving proliferation of many cell types.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is displayed at the cell surface where it encounters extracellular EGF-family ligands.
    action: ACCEPT
    reason: Primary surface localization supported by IDA; core. Retain over the REMOVE-tagged duplicate.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Internalized EGFR associates with endosomal membranes during its post-activation trafficking and downregulation.
    action: KEEP_AS_NON_CORE
    reason: Secondary trafficking-derived localization, not the primary functional site.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is a membrane protein, but the unqualified 'membrane' CC is uninformative when its plasma-membrane localization is established.
    action: MODIFY
    reason: Over-general CC parent; replace with plasma membrane.
    proposed_replacement_terms: *id001
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR localizes to the basolateral surface of polarized epithelia, consistent with its role in epithelial signaling.
    action: KEEP_AS_NON_CORE
    reason: Polarity-specific subdomain of the primary localization, supported by IDA but non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR binds numerous enzymes (kinases, phosphatases, ligases), but 'enzyme binding' is a generic catch-all conveying no specific function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative parent binding term; specific enzyme interactions captured elsewhere.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR interacts with kinases within signaling complexes, but 'kinase binding' is a generic uninformative term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative binding term, redundant with protein kinase binding.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0019903
    label: protein phosphatase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is bound and dephosphorylated by phosphatases (PTPN1/2/6, PTPRJ/K), but the generic binding term does not specify this regulatory relationship.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; the regulatory relationship is captured in process terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0030054
    label: cell junction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is detected at epithelial cell junctions where it intersects adhesion signaling.
    action: KEEP_AS_NON_CORE
    reason: Specialized localization linked to adhesion, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling promotes cell growth (mass increase) in responsive cells.
    action: KEEP_AS_NON_CORE
    reason: Downstream growth effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR (via CCDC88A/GIV and cytoskeletal remodeling) promotes cell migration, important in wound healing.
    action: KEEP_AS_NON_CORE
    reason: Downstream motility effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Activated EGFR binds CBL/CBLB and other E3 ligases (RNF115, RNF126) that ubiquitinate it for endosomal sorting and degradation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction central to receptor downregulation, but a regulatory partner binding rather than the core MF.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:0031901
    label: early endosome membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: After ligand-induced internalization EGFR resides on early endosome membranes, where sorting decisions (recycle vs degrade) shape signal duration.
    action: KEEP_AS_NON_CORE
    reason: Real post-activation trafficking compartment downstream of plasma-membrane signaling; not the primary site.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0032587
    label: ruffle membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Activated EGFR localizes to membrane ruffles during EGF-stimulated cytoskeletal remodeling and migration.
    action: KEEP_AS_NON_CORE
    reason: Migration-associated membrane subdomain, secondary to signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is part of signaling complexes, but the bare 'protein-containing complex' CC term is too generic; the receptor complex term is appropriate.
    action: MODIFY
    reason: Over-general cellular component; replace with receptor complex.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0033138
    label: positive regulation of peptidyl-serine phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling (via downstream Ser/Thr kinases) increases peptidyl-serine phosphorylation of targets.
    action: KEEP_AS_NON_CORE
    reason: Indirect downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0042177
    label: negative regulation of protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling can stabilize partner proteins, negatively regulating their catabolism.
    action: KEEP_AS_NON_CORE
    reason: Indirect downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0042327
    label: positive regulation of phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling increases phosphorylation of numerous downstream substrates.
    action: KEEP_AS_NON_CORE
    reason: Broad downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR homodimerizes, but the generic 'identical protein binding' term does not capture the receptor-dimerization mechanism meaningfully.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic term; dimerization is better captured by receptor complex/receptor-activity terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR-PI3K-AKT signaling promotes cell survival by suppressing apoptosis, e.g. in keratinocytes.
    action: KEEP_AS_NON_CORE
    reason: Pro-survival downstream effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Phosphorylated EGFR recruits GRB2/SOS to activate the RAS-RAF-MEK-ERK MAPK cascade.
    action: KEEP_AS_NON_CORE
    reason: Major downstream signaling output, but a regulatory effect downstream of the receptor's own activity.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR engages PI3K to activate AKT, a major pro-survival arm of its signaling.
    action: KEEP_AS_NON_CORE
    reason: Downstream effector pathway, non-core relative to receptor activity.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR partitions into membrane rafts/nanodomains that modulate its ligand binding and dimerization.
    action: KEEP_AS_NON_CORE
    reason: Regulatory membrane subdomain; refinement of plasma-membrane localization, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0045739
    label: positive regulation of DNA repair
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling can enhance DNA repair responses in some contexts.
    action: KEEP_AS_NON_CORE
    reason: Downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0045740
    label: positive regulation of DNA replication
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Mitogenic EGFR signaling promotes DNA replication during proliferation.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling (and nuclear EGFR) promotes Pol II transcription of target genes.
    action: KEEP_AS_NON_CORE
    reason: Downstream transcriptional output of signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Endosomal and Golgi-associated EGFR accumulates in the perinuclear region during trafficking.
    action: KEEP_AS_NON_CORE
    reason: Trafficking-derived localization, secondary to surface signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR drives proliferation of epithelial cells, central to epithelial development and homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific proliferative effect downstream of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0050730
    label: regulation of peptidyl-tyrosine phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR regulates tyrosine phosphorylation of substrates within its signaling network.
    action: KEEP_AS_NON_CORE
    reason: Regulatory framing of its kinase activity at the network level; non-core relative to the direct catalytic term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0051015
    label: actin filament binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR connects to the actin cytoskeleton during migration/ruffle formation, reported as actin filament binding.
    action: KEEP_AS_NON_CORE
    reason: Real cytoskeletal association supporting migration, but downstream of core kinase signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR activation positively drives the PI3K-AKT survival pathway.
    action: KEEP_AS_NON_CORE
    reason: Downstream regulatory effect of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0070141
    label: response to UV-A
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: UV-A can transactivate EGFR (ligand-independent activation), linking it to UV stress responses.
    action: KEEP_AS_NON_CORE
    reason: Stimulus-response role; transactivation context, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling activates the ERK1/2 (MAPK) cascade driving proliferative gene expression.
    action: KEEP_AS_NON_CORE
    reason: Downstream effector cascade activation, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0071392
    label: cellular response to estradiol stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR participates in cellular responses to estradiol, partly via GPER1-dependent transactivation.
    action: KEEP_AS_NON_CORE
    reason: Stimulus-response role, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
- term:
    id: GO:0090037
    label: positive regulation of protein kinase C signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Via PLCgamma activation EGFR drives PKC signaling.
    action: KEEP_AS_NON_CORE
    reason: Downstream effector arm, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling can positively modulate canonical Wnt signaling via cross-talk.
    action: KEEP_AS_NON_CORE
    reason: Pathway cross-talk effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0097489
    label: multivesicular body, internal vesicle lumen
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR sorted for degradation is delivered into the internal vesicles of multivesicular bodies via the ESCRT machinery.
    action: KEEP_AS_NON_CORE
    reason: Degradation-pathway localization downstream of activation, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0097708
    label: intracellular vesicle
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is found in intracellular vesicles of the endocytic/trafficking system after internalization.
    action: KEEP_AS_NON_CORE
    reason: Generic trafficking compartment, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0098609
    label: cell-cell adhesion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR intersects cell-cell adhesion through cross-talk with junctional and adhesion molecules.
    action: KEEP_AS_NON_CORE
    reason: Adhesion-related role downstream of/parallel to signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:1900087
    label: positive regulation of G1/S transition of mitotic cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR mitogenic signaling drives cell-cycle G1/S progression.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:1902895
    label: positive regulation of miRNA transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling promotes transcription of specific miRNAs.
    action: KEEP_AS_NON_CORE
    reason: Downstream transcriptional effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:1903078
    label: positive regulation of protein localization to plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling promotes recruitment/retention of partner proteins at the plasma membrane.
    action: KEEP_AS_NON_CORE
    reason: Downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:1905208
    label: negative regulation of cardiocyte differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling negatively regulates cardiomyocyte differentiation during heart development.
    action: KEEP_AS_NON_CORE
    reason: Cardiac developmental role downstream of signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR has been reported in the nucleolus in specific contexts within its nuclear pool.
    action: KEEP_AS_NON_CORE
    reason: Rare context-specific localization, secondary to canonical signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0018108
    label: peptidyl-tyrosine phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR phosphorylates tyrosine residues on itself and on substrate proteins (e.g. EPS8, EPS15), the biochemical process of its kinase activity.
    action: ACCEPT
    reason: Direct enzymatic process term matching the catalytic MF; retain as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0046777
    label: protein autophosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Upon ligand-induced dimerization EGFR autophosphorylates C-terminal tail tyrosines (e.g. Y1092, Y1110, Y1172), creating docking sites for downstream adaptors.
    action: ACCEPT
    reason: Defining direct catalytic output of the activated receptor, supported by IDA.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0097225
    label: sperm midpiece
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is detected in the sperm midpiece in spermatozoa.
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific localization, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0097228
    label: sperm principal piece
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is detected in the sperm flagellar principal piece.
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific localization, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0097229
    label: sperm end piece
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is detected in the sperm flagellar end piece, a tissue-specific localization.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific localization unrelated to core epithelial signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR is itself the signaling receptor and engages receptor partners, but this term is too generic to describe its function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Non-informative binding term; receptor role captured by receptor-activity MF.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0005178
    label: integrin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR cross-talks with integrins, and integrin binding links it to adhesion-dependent signaling.
    action: KEEP_AS_NON_CORE
    reason: Real adhesion-related interaction, secondary to core kinase signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:0005516
    label: calmodulin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR's juxtamembrane region binds calmodulin, a Ca2+-dependent modulator of receptor activity.
    action: KEEP_AS_NON_CORE
    reason: Real regulatory interaction, but not the core MF of the receptor.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Activated EGFR is endocytosed into endosomes from which it can continue signaling before recycling or lysosomal degradation.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization arising from receptor trafficking, downstream of surface signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR signaling and trafficking intermediates are detected in the cytosol.
    action: KEEP_AS_NON_CORE
    reason: Generic secondary localization, not the primary functional site.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005929
    label: cilium
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR has been reported at the cilium in some cell types.
    action: KEEP_AS_NON_CORE
    reason: Context-specific localization, not core to receptor signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0006412
    label: translation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR is a receptor tyrosine kinase with no role in the process of mRNA translation; this ISO-projected term is biologically implausible.
    action: REMOVE
    reason: No mechanistic basis; EGFR does not function in translation. Likely erroneous electronic projection.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007611
    label: learning or memory
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR enhances learning and memory performance, a pleiotropic neural role.
    action: KEEP_AS_NON_CORE
    reason: Behavioral/physiological role downstream of neural EGFR signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR is displayed at the cell surface where it encounters extracellular EGF-family ligands.
    action: ACCEPT
    reason: Primary surface localization supported by IDA; core. Retain over the REMOVE-tagged duplicate.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR localizes to the basolateral surface of polarized epithelia, consistent with its role in epithelial signaling.
    action: KEEP_AS_NON_CORE
    reason: Polarity-specific subdomain of the primary localization, supported by IDA but non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: In polarized epithelia EGFR can localize to the apical plasma-membrane domain.
    action: KEEP_AS_NON_CORE
    reason: Polarity-specific subdomain of its primary localization; non-core specialization.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR contacts various protein kinases (e.g. SRC-family) but the generic 'protein kinase binding' term adds no specific functional detail.
    action: MARK_AS_OVER_ANNOTATED
    reason: Non-informative binding parent; specific roles captured elsewhere.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0019903
    label: protein phosphatase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR is bound and dephosphorylated by phosphatases (PTPN1/2/6, PTPRJ/K), but the generic binding term does not specify this regulatory relationship.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; the regulatory relationship is captured in process terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0030139
    label: endocytic vesicle
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Ligand-activated EGFR is captured in endocytic vesicles during clathrin-mediated internalization.
    action: KEEP_AS_NON_CORE
    reason: Trafficking-intermediate localization downstream of activation at the surface.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0032930
    label: positive regulation of superoxide anion generation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR signaling can stimulate NADPH-oxidase-dependent superoxide generation.
    action: KEEP_AS_NON_CORE
    reason: Downstream signaling effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR initiates intracellular signal transduction cascades upon activation.
    action: KEEP_AS_NON_CORE
    reason: Generic downstream process, non-core relative to the specific EGFR pathway.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGFR is reported at the ciliary basal body in some contexts.
    action: KEEP_AS_NON_CORE
    reason: Specialized localization, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0042311
    label: vasodilation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR signaling participates in vascular vasodilation responses.
    action: KEEP_AS_NON_CORE
    reason: Vascular physiological effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic and physiological evidence also implicates EGFR in **bone/endochondral ossification** and **heart valve** development.
- term:
    id: GO:0042698
    label: ovulation cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR signaling participates in the ovulation cycle (cumulus expansion/ovulation).
    action: KEEP_AS_NON_CORE
    reason: Reproductive physiology process downstream of signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic and physiological evidence also implicates EGFR in **bone/endochondral ossification** and **heart valve** development.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR-PI3K-AKT signaling promotes cell survival by suppressing apoptosis, e.g. in keratinocytes.
    action: KEEP_AS_NON_CORE
    reason: Pro-survival downstream effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Phosphorylated EGFR recruits GRB2/SOS to activate the RAS-RAF-MEK-ERK MAPK cascade.
    action: KEEP_AS_NON_CORE
    reason: Major downstream signaling output, but a regulatory effect downstream of the receptor's own activity.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR associates with multiprotein complexes, but this generic binding term provides no specific functional information.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; complex membership is captured by receptor complex.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0045780
    label: positive regulation of bone resorption
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR signaling promotes osteoclast-mediated bone resorption.
    action: KEEP_AS_NON_CORE
    reason: Skeletal physiology effect downstream of signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic and physiological evidence also implicates EGFR in **bone/endochondral ossification** and **heart valve** development.
- term:
    id: GO:0045907
    label: positive regulation of vasoconstriction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR transactivation (e.g. by GPCR agonists) contributes to vasoconstriction.
    action: KEEP_AS_NON_CORE
    reason: Vascular physiological effect downstream of signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic and physiological evidence also implicates EGFR in **bone/endochondral ossification** and **heart valve** development.
- term:
    id: GO:0045930
    label: negative regulation of mitotic cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: In some contexts EGFR signaling negatively regulates the mitotic cell cycle.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent downstream cell-cycle effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0048143
    label: astrocyte activation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR signaling contributes to astrocyte activation in the CNS.
    action: KEEP_AS_NON_CORE
    reason: Glial physiological role, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:0048408
    label: epidermal growth factor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: The EGFR extracellular L-domains directly bind EGF and other EGF-family ligands, the event that triggers receptor dimerization and activation.
    action: ACCEPT
    reason: Core ligand-binding MF supported by IDA; central to receptor function.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0048661
    label: positive regulation of smooth muscle cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR signaling drives smooth muscle cell proliferation, e.g. in vascular remodeling.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific proliferative effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0048812
    label: neuron projection morphogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR signaling shapes neuron projection morphogenesis.
    action: KEEP_AS_NON_CORE
    reason: Neural developmental role, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:0051592
    label: response to calcium ion
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR participates in cellular responses to calcium ion signaling.
    action: KEEP_AS_NON_CORE
    reason: Stimulus-response role, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
- term:
    id: GO:0051968
    label: positive regulation of synaptic transmission, glutamatergic
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR positively modulates glutamatergic synaptic transmission.
    action: KEEP_AS_NON_CORE
    reason: Neuronal physiological effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:0060252
    label: positive regulation of glial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR promotes proliferation of glial cells in the CNS.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific proliferative effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0070257
    label: positive regulation of mucus secretion
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR drives mucin/mucus secretion in epithelial (e.g. airway) tissue.
    action: KEEP_AS_NON_CORE
    reason: Epithelial secretory effect downstream of signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic and physiological evidence also implicates EGFR in **bone/endochondral ossification** and **heart valve** development.
- term:
    id: GO:0071364
    label: cellular response to epidermal growth factor stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: As the EGF receptor, EGFR mediates the cellular response to EGF stimulus.
    action: KEEP_AS_NON_CORE
    reason: Response-to-stimulus framing of its core function; per principles, response-to-X terms are non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
- term:
    id: GO:0097060
    label: synaptic membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR is found at synaptic membranes consistent with neuronal signaling roles in learning/memory.
    action: KEEP_AS_NON_CORE
    reason: Neuron-specific localization downstream of EGFR's pleiotropic neural function.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:0097421
    label: liver regeneration
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR mitogenic signaling drives hepatocyte proliferation during liver regeneration.
    action: KEEP_AS_NON_CORE
    reason: Organ-level physiological process downstream of proliferative signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic and physiological evidence also implicates EGFR in **bone/endochondral ossification** and **heart valve** development.
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR localizes to glutamatergic synapses where it modulates synaptic transmission.
    action: KEEP_AS_NON_CORE
    reason: Neuron-specific localization, downstream pleiotropic role.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:1902722
    label: positive regulation of prolactin secretion
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: EGFR signaling promotes prolactin secretion in endocrine contexts.
    action: KEEP_AS_NON_CORE
    reason: Endocrine physiological effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic and physiological evidence also implicates EGFR in **bone/endochondral ossification** and **heart valve** development.
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IMP
  original_reference_id: PMID:28790147
  review:
    summary: EGFR signaling alters gene expression programs controlling proliferation and survival.
    action: KEEP_AS_NON_CORE
    reason: Very broad downstream process; non-core (and over-general), retained as pleiotropic effect.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0042908
    label: xenobiotic transport
  evidence_type: IMP
  original_reference_id: PMID:28790147
  review:
    summary: Altered xenobiotic transport in Egfr-perturbed cells is a distal phenotype (e.g. EGFR-dependent regulation of transporter expression), not a direct EGFR activity.
    action: KEEP_AS_NON_CORE
    reason: Downstream phenotype of EGFR signaling; non-core (experimental IMP retained, not removed).
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22975324
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:21946538
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: ISO
  original_reference_id: PMID:11894095
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0042059
    label: negative regulation of epidermal growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: PMID:11894095
  review:
    summary: EGFR signaling is subject to feedback downregulation (CBL-mediated ubiquitination, endocytosis, LRIG1/ERRFI1/SOCS feedback inhibitors).
    action: KEEP_AS_NON_CORE
    reason: Regulatory/feedback process on its own pathway, supported by IDA/IMP but non-core to the receptor's MF.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:15962011
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:11823423
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:15383614
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IDA
  original_reference_id: PMID:11823423
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0042059
    label: negative regulation of epidermal growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:11823423
  review:
    summary: EGFR signaling is subject to feedback downregulation (CBL-mediated ubiquitination, endocytosis, LRIG1/ERRFI1/SOCS feedback inhibitors).
    action: KEEP_AS_NON_CORE
    reason: Regulatory/feedback process on its own pathway, supported by IDA/IMP but non-core to the receptor's MF.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:15383614
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:23457600
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IDA
  original_reference_id: PMID:23457600
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:15383614
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0042059
    label: negative regulation of epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:23457600
  review:
    summary: EGFR signaling is subject to feedback downregulation (CBL-mediated ubiquitination, endocytosis, LRIG1/ERRFI1/SOCS feedback inhibitors).
    action: KEEP_AS_NON_CORE
    reason: Regulatory/feedback process on its own pathway, supported by IDA/IMP but non-core to the receptor's MF.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ubiquitination is a key biochemical tag that couples receptor activation to downregulation.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: PMID:15611079
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: ISO
  original_reference_id: PMID:2472218
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: ISO
  original_reference_id: PMID:9890893
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: ISO
  original_reference_id: PMID:2176151
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IDA
  original_reference_id: PMID:9529375
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:12761849
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: PMID:9890893
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IDA
  original_reference_id: PMID:7678348
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:6248866
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:7678348
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:8702723
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:7678348
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:21897861
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:21897861
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:21897861
  review:
    summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling.
    action: ACCEPT
    reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: ISO
  original_reference_id: PMID:11336639
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IMP
  original_reference_id: PMID:18701712
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: PMID:11336639
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: ISO
  original_reference_id: PMID:11336639
  review:
    summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling.
    action: ACCEPT
    reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:18701712
  review:
    summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling.
    action: ACCEPT
    reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:9556621
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:8702723
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:8702723
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:8702723
  review:
    summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling.
    action: ACCEPT
    reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:12399441
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IGI
  original_reference_id: PMID:28783046
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:8456283
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IGI
  original_reference_id: PMID:28783046
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:8456283
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:9556621
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:12399441
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:28783046
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:8456283
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:9556621
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:9556621
  review:
    summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling.
    action: ACCEPT
    reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:23333074
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:23899604
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:30770250
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:7752576
  review:
    summary: EGFR is a single-pass type I transmembrane receptor whose intracellular kinase domain phosphorylates protein tyrosines upon EGF-family ligand binding; this is its defining catalytic/receptor activity.
    action: ACCEPT
    reason: Most specific, correct MF for a receptor tyrosine kinase; directly supported by IDA/IMP and the EC 2.7.10.1 reaction.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:28494873
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:7752576
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:8621573
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:23333074
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:23899604
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:30770250
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:7752576
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IGI
  original_reference_id: PMID:16357442
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IDA
  original_reference_id: PMID:21946538
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:21946538
  review:
    summary: EGFR forms heterodimers with ERBB2, and the ERBB2-EGFR heterodimer is a principal signaling-competent complex driving proliferative signaling.
    action: ACCEPT
    reason: Direct, defining signaling output via the documented ERBB2 heterodimer (SUBUNIT); supported by IDA/IMP.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IDA
  original_reference_id: PMID:6248866
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IDA
  original_reference_id: PMID:7752576
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:6248866
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15695332
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15728722
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:1902966
    label: positive regulation of protein localization to early endosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: EGFR activation drives recruitment of sorting machinery to early endosomes during its trafficking.
    action: KEEP_AS_NON_CORE
    reason: Trafficking-associated regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IDA
  original_reference_id: PMID:11940581
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: IDA
  original_reference_id: PMID:8702723
  review:
    summary: EGFR mediates cellular responses to EGF-family growth factor stimuli.
    action: KEEP_AS_NON_CORE
    reason: Broad response-to-stimulus term, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: EGFR signaling promotes cell growth (mass increase) in responsive cells.
    action: KEEP_AS_NON_CORE
    reason: Downstream growth effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0048408
    label: epidermal growth factor binding
  evidence_type: IDA
  original_reference_id: PMID:7678348
  review:
    summary: The EGFR extracellular L-domains directly bind EGF and other EGF-family ligands, the event that triggers receptor dimerization and activation.
    action: ACCEPT
    reason: Core ligand-binding MF supported by IDA; central to receptor function.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15467833
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0001942
    label: hair follicle development
  evidence_type: IGI
  original_reference_id: PMID:9030684
  review:
    summary: EGFR signaling is required for normal hair follicle development (e.g. waved-2 phenotype).
    action: KEEP_AS_NON_CORE
    reason: Tissue-development role downstream of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0061029
    label: eyelid development in camera-type eye
  evidence_type: IGI
  original_reference_id: PMID:9030684
  review:
    summary: EGFR signaling is required for eyelid morphogenesis (open-eyelid phenotypes in pathway mutants).
    action: KEEP_AS_NON_CORE
    reason: Organ-development role downstream of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25744720
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IDA
  original_reference_id: PMID:23918928
  review:
    summary: EGFR is displayed at the cell surface where it encounters extracellular EGF-family ligands.
    action: ACCEPT
    reason: Primary surface localization supported by IDA; core. Retain over the REMOVE-tagged duplicate.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0043235
    label: receptor complex
  evidence_type: ISO
  original_reference_id: PMID:23382219
  review:
    summary: Active EGFR exists as a ligand-induced homo- or heterodimeric receptor complex (e.g. with ERBB2), the signaling-competent unit.
    action: ACCEPT
    reason: Captures the functional dimeric receptor assembly; core CC supported by IBA/ISO.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0071230
    label: cellular response to amino acid stimulus
  evidence_type: IDA
  original_reference_id: PMID:22711986
  review:
    summary: EGFR mediates cellular responses to amino acid stimulus in nutrient signaling contexts.
    action: KEEP_AS_NON_CORE
    reason: Stimulus-response role, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
- term:
    id: GO:0001934
    label: positive regulation of protein phosphorylation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Active EGFR promotes phosphorylation of effector proteins in its signaling network.
    action: KEEP_AS_NON_CORE
    reason: Broad downstream regulatory effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Nuclear EGFR has been reported to bind chromatin and act as a transcriptional co-regulator in specific contexts.
    action: KEEP_AS_NON_CORE
    reason: Non-canonical activity of the nuclear pool, downstream of canonical signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: 'Mouse evidence supports a non-redundant role of EGFR in kidney epithelial physiology: EGFR impairment is associated with collecting-duct abnormalities, and collecting-duct–specific EGFR deletion can cause **thin medulla**, **polyuria**, and impaired urine concentrating ability.'
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: EGFR signaling (and nuclear EGFR) promotes Pol II transcription of target genes.
    action: KEEP_AS_NON_CORE
    reason: Downstream transcriptional output of signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: EGFR signaling activates the ERK1/2 (MAPK) cascade driving proliferative gene expression.
    action: KEEP_AS_NON_CORE
    reason: Downstream effector cascade activation, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0071392
    label: cellular response to estradiol stimulus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: EGFR participates in cellular responses to estradiol, partly via GPER1-dependent transactivation.
    action: KEEP_AS_NON_CORE
    reason: Stimulus-response role, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR activation can occur via ligand binding or via transactivation pathways (e.g., UVB- and cytokine-linked inputs).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17726113
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20208556
  review:
    summary: A pool of EGFR translocates to the nucleus (via Golgi/ER, aided by PIKFYVE) where it can influence transcription in specific contexts.
    action: KEEP_AS_NON_CORE
    reason: Context-specific non-canonical localization, secondary to membrane signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: IMP
  original_reference_id: PMID:20208556
  review:
    summary: EGFR signaling stimulates fibroblast proliferation.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific proliferative effect, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:20208556
  review:
    summary: Endosomal and Golgi-associated EGFR accumulates in the perinuclear region during trafficking.
    action: KEEP_AS_NON_CORE
    reason: Trafficking-derived localization, secondary to surface signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Activated EGFR is endocytosed into endosomes from which it can continue signaling before recycling or lysosomal degradation.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization arising from receptor trafficking, downstream of surface signaling.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
- term:
    id: GO:0004888
    label: transmembrane signaling receptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: EGFR is a transmembrane signaling receptor, but more precisely a receptor tyrosine kinase that couples ligand binding to intrinsic catalytic activity.
    action: MODIFY
    reason: Correct but too general a receptor MF; replace with the kinase-coupled RTK term capturing the catalytic mechanism.
    proposed_replacement_terms: *id003
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: EGFR signals via a cell-surface receptor signaling pathway; the EGFR-specific term captures the precise function.
    action: KEEP_AS_NON_CORE
    reason: Over-general parent of the specific EGFR pathway; keep as non-core rather than removing.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: EGFR is a mitogenic receptor driving proliferation of many cell types.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16120644
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: EGFR catalyzes transfer of the gamma-phosphate of ATP to tyrosine residues of substrate proteins (EC 2.7.10.1), including autophosphorylation of its own C-terminal tail.
    action: ACCEPT
    reason: Correct catalytic MF supported by IDA/IMP; appropriately specific for a Tyr kinase, retained as core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0001892
    label: embryonic placenta development
  evidence_type: IMP
  original_reference_id: PMID:7618084
  review:
    summary: EGFR is essential for placental development; embryonic lethality in Egfr-null mice is due to placental defects.
    action: KEEP_AS_NON_CORE
    reason: Developmental role downstream of receptor signaling, non-core but biologically important.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0001942
    label: hair follicle development
  evidence_type: IMP
  original_reference_id: PMID:7618084
  review:
    summary: EGFR signaling is required for normal hair follicle development (e.g. waved-2 phenotype).
    action: KEEP_AS_NON_CORE
    reason: Tissue-development role downstream of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0008544
    label: epidermis development
  evidence_type: IMP
  original_reference_id: PMID:7618084
  review:
    summary: EGFR is required for epidermal development; loss causes skin barrier defects and dermatitis.
    action: KEEP_AS_NON_CORE
    reason: Organ-development role downstream of EGFR's proliferative/survival signaling; pleiotropic, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0021795
    label: cerebral cortex cell migration
  evidence_type: IMP
  original_reference_id: PMID:7618084
  review:
    summary: EGFR signaling influences migration of cells in the developing cerebral cortex.
    action: KEEP_AS_NON_CORE
    reason: Developmental neuronal migration role, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0048546
    label: digestive tract morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:7618084
  review:
    summary: EGFR is required for normal gastrointestinal tract morphogenesis; Egfr-null mice show gut defects.
    action: KEEP_AS_NON_CORE
    reason: Organ-development role downstream of epithelial signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:7618084
  review:
    summary: EGFR drives proliferation of epithelial cells, central to epithelial development and homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific proliferative effect downstream of receptor signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0060571
    label: morphogenesis of an epithelial fold
  evidence_type: IMP
  original_reference_id: PMID:7618084
  review:
    summary: EGFR-driven epithelial proliferation contributes to morphogenesis of epithelial folds.
    action: KEEP_AS_NON_CORE
    reason: Morphogenetic role downstream of epithelial signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0000902
    label: cell morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:17686994
  review:
    summary: EGFR signaling influences cell shape/morphogenesis during development.
    action: KEEP_AS_NON_CORE
    reason: Broad developmental morphogenesis effect, non-core; not contradicted, so retain rather than REMOVE.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:17686994
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0007435
    label: salivary gland morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:10521784
  review:
    summary: EGFR is required for branching morphogenesis of the salivary gland.
    action: KEEP_AS_NON_CORE
    reason: Organ-morphogenesis role downstream of epithelial EGFR signaling, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Mouse genetic evidence supports EGFR as an essential regulator of **epithelial organ development** and **postnatal epithelial homeostasis**.
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:11818567
  review:
    summary: EGFR regulates proliferation of target cell populations.
    action: KEEP_AS_NON_CORE
    reason: Broad regulatory proliferation term, non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:18656477
  review:
    summary: EGFR is a mitogenic receptor driving proliferation of many cell types.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:7641815
  review:
    summary: EGFR is a type I plasma-membrane receptor; the cell surface is its primary site of ligand binding and signal initiation.
    action: ACCEPT
    reason: Primary, defining localization supported by IDA/IBA/IGI; core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:7641815
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:7641815
  review:
    summary: EGFR is a mitogenic receptor driving proliferation of many cell types.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0046777
    label: protein autophosphorylation
  evidence_type: IDA
  original_reference_id: PMID:15314156
  review:
    summary: Upon ligand-induced dimerization EGFR autophosphorylates C-terminal tail tyrosines (e.g. Y1092, Y1110, Y1172), creating docking sites for downstream adaptors.
    action: ACCEPT
    reason: Defining direct catalytic output of the activated receptor, supported by IDA.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:15695332
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  evidence_type: IDA
  original_reference_id: PMID:14712229
  review:
    summary: 'EGFR is the prototypical EGF-family ligand receptor: it binds EGF/TGFA and transduces the signal via its tyrosine kinase activity, the textbook function of this gene.'
    action: ACCEPT
    reason: Defining receptor MF, supported by IDA/IMP. Retain the REMOVE-tagged duplicate as a single accepted core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: '**Egfr** encodes EGFR, the prototypical member of the **ErbB family** of receptor tyrosine kinases.'
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:14712229
  review:
    summary: EGFR is the initiating receptor of the EGFR signaling pathway, converting EGF-family ligand binding into downstream RAS-MAPK, PI3K-AKT, PLCgamma and STAT signaling.
    action: ACCEPT
    reason: Defining direct signaling output of the gene; supported by IDA/IMP/IGI. Retain as single core term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Autophosphorylation then recruits adaptors/effectors (e.g., Shc/Grb2/SOS1, Gab1, SHP2, PI3K) that initiate pathway cascades including MAPK and PI3K–AKT.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:14712229
  review:
    summary: EGFR is a mitogenic receptor driving proliferation of many cell types.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect (broad); non-core. Retain over the REMOVE-tagged duplicate.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: In mouse skin, EGFR supports **keratinocyte survival, proliferation, migration, and wound healing**, with emphasis on PI3K–AKT for anti-apoptotic survival and EGFR–MEK–ERK for proliferation/migration in keratinocytes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12919676
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:7723235
  review:
    summary: EGFR localizes to the basolateral surface of polarized epithelia, consistent with its role in epithelial signaling.
    action: KEEP_AS_NON_CORE
    reason: Polarity-specific subdomain of the primary localization, supported by IDA but non-core.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is primarily a **plasma-membrane** receptor that is dynamically redistributed to **endosomes** after activation and has been reported to access **nuclear** and **mitochondrial** pools in some contexts.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IDA
  original_reference_id: PMID:12808090
  review:
    summary: EGFR has kinase activity, but the unqualified term loses the tyrosine/receptor specificity that defines EGFR.
    action: MODIFY
    reason: Over-general parent of the catalytic MF; replace with transmembrane receptor protein tyrosine kinase activity.
    proposed_replacement_terms:
    - id: GO:0004714
      label: transmembrane receptor protein tyrosine kinase activity
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IDA
  original_reference_id: PMID:11940581
  review:
    summary: EGFR is a signal transducer, but this top-level process term is uninformative when the specific EGFR signaling pathway is annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-general process parent; specific EGFR signaling pathway captured separately.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0050730
    label: regulation of peptidyl-tyrosine phosphorylation
  evidence_type: IMP
  original_reference_id: PMID:11940581
  review:
    summary: EGFR regulates tyrosine phosphorylation of substrates within its signaling network.
    action: KEEP_AS_NON_CORE
    reason: Regulatory framing of its kinase activity at the network level; non-core relative to the direct catalytic term.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: Ligand binding promotes receptor dimerization and stabilizes an active intracellular kinase configuration (often described as an **asymmetric kinase dimer**) that drives autophosphorylation of the C-terminal tail.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11274221
  review:
    summary: EGFR engages many partners (GRB2, CBL, STAT3, ERBB2, etc.), but the bare 'protein binding' term conveys no specific molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative IPI term; specific interactions are captured by named-partner or complex terms.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
- term:
    id: GO:0030139
    label: endocytic vesicle
  evidence_type: IDA
  original_reference_id: PMID:10534613
  review:
    summary: Ligand-activated EGFR is captured in endocytic vesicles during clathrin-mediated internalization.
    action: KEEP_AS_NON_CORE
    reason: Trafficking-intermediate localization downstream of activation at the surface.
    supported_by:
    - reference_id: UniProt:Q01279
      supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
    - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
      supporting_text: EGFR is internalized via **clathrin-mediated endocytosis** as well as **non-clathrin (e.g., caveolar) routes**.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000008
  title: Gene Ontology annotation by the MGI curatorial staff, curated orthology
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10521784
  title: '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.'
  findings: []
- id: PMID:10534613
  title: Ectodysplasin, a protein required for epithelial morphogenesis, is a novel TNF homologue and promotes cell-matrix adhesion.
  findings: []
- id: PMID:11274221
  title: 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.
  findings: []
- id: PMID:11336639
  title: Heterodimerization of the epidermal-growth-factor (EGF) receptor and ErbB2 and the affinity of EGF binding are regulated by different mechanisms.
  findings: []
- id: PMID:11818567
  title: Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis.
  findings: []
- id: PMID:11823423
  title: A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.
  findings: []
- id: PMID:11894095
  title: Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors.
  findings: []
- id: PMID:11940581
  title: 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.
  findings: []
- id: PMID:12399441
  title: ErbB signaling regulates lineage determination of developing pancreatic islet cells in embryonic organ culture.
  findings: []
- id: PMID:12761849
  title: EGF-stimulated signaling by means of PI3K, PLCgamma1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular gland.
  findings: []
- id: PMID:12808090
  title: Gab1 is an integrator of cell death versus cell survival signals in oxidative stress.
  findings: []
- id: PMID:12919676
  title: CAML is required for efficient EGF receptor recycling.
  findings: []
- id: PMID:14712229
  title: 'G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway.'
  findings: []
- id: PMID:15314156
  title: MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met.
  findings: []
- id: PMID:15383614
  title: c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15.
  findings: []
- id: PMID:15467833
  title: CEACAM1 modulates epidermal growth factor receptor--mediated cell proliferation.
  findings: []
- id: PMID:15611079
  title: Epigen, the last ligand of ErbB receptors, reveals intricate relationships between affinity and mitogenicity.
  findings: []
- id: PMID:15695332
  title: Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling.
  findings: []
- id: PMID:15728722
  title: 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.
  findings: []
- id: PMID:15962011
  title: Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation.
  findings: []
- id: PMID:16120644
  title: Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes.
  findings: []
- id: PMID:16357442
  title: Soluble form of heparin-binding EGF-like growth factor contributes to retinoic acid-induced epidermal hyperplasia.
  findings: []
- id: PMID:16954185
  title: Advanced glycation end product (AGE) receptor 1 suppresses cell oxidant stress and activation signaling via EGF receptor.
  findings: []
- id: PMID:17686994
  title: The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskeleton through activation of the ephrin pathway.
  findings: []
- id: PMID:17726113
  title: Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models.
  findings: []
- id: PMID:18656477
  title: Betacellulin stimulates growth of the mouse intestinal epithelium and increases adenoma multiplicity in Apc+/Min mice.
  findings: []
- id: PMID:18701712
  title: Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis.
  findings: []
- id: PMID:20208556
  title: Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7.
  findings: []
- id: PMID:21439278
  title: Engineered epidermal growth factor mutants with faster binding on-rates correlate with enhanced receptor activation.
  findings: []
- id: PMID:2176151
  title: The tyrosine phosphorylated carboxyterminus of the EGF receptor is a binding site for GAP and PLC-gamma.
  findings: []
- id: PMID:21897861
  title: Betacellulin-induced beta cell proliferation and regeneration is mediated by activation of ErbB-1 and ErbB-2 receptors.
  findings: []
- id: PMID:21946538
  title: Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis.
  findings: []
- id: PMID:22711986
  title: Calpain 2 activated through N-methyl-D-aspartic acid receptor signaling cleaves CPEB3 and abrogates CPEB3-repressed translation in neurons.
  findings: []
- id: PMID:22975324
  title: Mig6 is a sensor of EGF receptor inactivation that directly activates c-Abl to induce apoptosis during epithelial homeostasis.
  findings: []
- id: PMID:22975374
  title: EGF receptor is required for KRAS-induced pancreatic tumorigenesis.
  findings: []
- id: PMID:23333074
  title: Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor.
  findings: []
- id: PMID:23382219
  title: Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.
  findings: []
- id: PMID:23457600
  title: Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells.
  findings: []
- id: PMID:23799367
  title: Threshold-controlled ubiquitination of the EGFR directs receptor fate.
  findings: []
- id: PMID:23899604
  title: Increased activation of the epidermal growth factor receptor in transgenic mice overexpressing epigen causes peripheral neuropathy.
  findings: []
- id: PMID:23918928
  title: Furin is the primary in vivo convertase of angiopoietin-like 3 and endothelial lipase in hepatocytes.
  findings: []
- id: PMID:2472218
  title: 'EGF induces tyrosine phosphorylation of phospholipase C-II: a potential mechanism for EGF receptor signaling.'
  findings: []
- id: PMID:25744720
  title: Lung Tumor Suppressor GPRC5A Binds EGFR and Restrains Its Effector Signaling.
  findings: []
- id: PMID:28494873
  title: A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In Vivo.
  findings: []
- id: PMID:28783046
  title: Epiregulin and EGFR interactions are involved in pain processing.
  findings: []
- id: PMID:28790147
  title: Hepatocyte-Specific Deletion of EGFR in Mice Reduces Hepatic Abcg2 Transport Activity Measured by [(11)C]erlotinib and Positron Emission Tomography.
  findings: []
- id: PMID:30770250
  title: A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation.
  findings: []
- id: PMID:6248866
  title: Detection of epidermal growth factor-urogastrone and its receptor during fetal mouse development.
  findings: []
- id: PMID:7618084
  title: 'Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype.'
  findings: []
- id: PMID:7641815
  title: Altering the expression of cell surface beta 1,4-galactosyltransferase modulates cell growth.
  findings: []
- id: PMID:7678348
  title: Expression of the epidermal growth factor receptor gene is regulated in mouse blastocysts during delayed implantation.
  findings: []
- id: PMID:7723235
  title: Epidermal growth factor receptor expression is abnormal in murine polycystic kidney.
  findings: []
- id: PMID:7752576
  title: Tyrosine kinase activity of the EGF receptor in murine metanephric organ culture.
  findings: []
- id: PMID:8456283
  title: 'Betacellulin: a mitogen from pancreatic beta cell tumors.'
  findings: []
- id: PMID:8621573
  title: STAT activation by epidermal growth factor (EGF) and amphiregulin. Requirement for the EGF receptor kinase but not for tyrosine phosphorylation sites or JAK1.
  findings: []
- id: PMID:8702723
  title: The epidermal growth factor receptor couples transforming growth factor-alpha, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4.
  findings: []
- id: PMID:9030684
  title: Mutation in Sos1 dominantly enhances a weak allele of the EGFR, demonstrating a requirement for Sos1 in EGFR signaling and development.
  findings: []
- id: PMID:9529375
  title: Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse embryonic fibroblasts.
  findings: []
- id: PMID:9556621
  title: Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2.
  findings: []
- id: PMID:9890893
  title: Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro.
  findings: []
- id: UniProt:Q01279
  title: UniProt record for Egfr (Q01279)
  findings: []
- id: file:mouse/Egfr/Egfr-bioreason-rl-predictions.md
  title: Deep research report on Egfr (bioreason)
  findings: []
- id: file:mouse/Egfr/Egfr-bioreason-rl-predictions.md
  title: Deep research report on Egfr (bioreason-rl)
  findings: []
- id: file:mouse/Egfr/Egfr-deep-research-falcon.md
  title: Deep research report on Egfr (falcon)
  findings: []
core_functions:
- molecular_function:
    id: GO:0005006
    label: epidermal growth factor receptor activity
  description: Binds EGF-family ligands as a cell-surface receptor and converts ligand binding into receptor dimerization, autophosphorylation, and recruitment of signaling adaptors.
  locations:
  - id: GO:0005886
    label: plasma membrane
  directly_involved_in:
  - id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  supported_by:
  - reference_id: UniProt:Q01279
    supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
  - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
    supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
  in_complex:
    id: GO:0043235
    label: receptor complex
- molecular_function:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  description: Uses its intracellular kinase domain to phosphorylate tyrosine residues on itself and downstream substrates after ligand-induced activation.
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0005768
    label: endosome
  directly_involved_in:
  - id: GO:0046777
    label: protein autophosphorylation
  - id: GO:0018108
    label: peptidyl-tyrosine phosphorylation
  supported_by:
  - reference_id: UniProt:Q01279
    supporting_text: 'FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation. CATALYTIC ACTIVITY: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endocytosed upon activation by ligand.'
  - reference_id: file:mouse/Egfr/Egfr-deep-research-falcon.md
    supporting_text: EGFR is a **protein-tyrosine kinase** whose core catalytic function is to **transfer the γ-phosphate from ATP to tyrosine residues** on protein substrates.
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []

Gene Description

Existing Annotations Review

Core Functions

Binds EGF-family ligands as a cell-surface receptor and converts ligand binding into receptor dimerization, autophosphorylation, and recruitment of signaling adaptors.

Uses its intracellular kinase domain to phosphorylate tyrosine residues on itself and downstream substrates after ligand-induced activation.

References

Deep Research

Falcon

Research Report: Mouse Egfr (EGFR/ErbB1) — Functional Annotation (UniProt Q01279)

0) Target verification (mandatory)

1) Key concepts and definitions (current understanding)

1.1 What Egfr encodes

1.2 EGFR as an enzyme: reaction and substrate specificity

1.3 Canonical EGFR phosphosites used as docking platforms

1.4 Signaling outputs: pathway definitions

2) Molecular mechanism: activation, signaling, and localization

2.1 Activation mechanism and coupling to docking-site formation

2.2 Subcellular localization and trafficking as a control layer

2.3 Ubiquitination/ESCRT axis as a mechanistic switch for signal termination

3) Mouse-specific physiology and in vivo functional annotation

3.1 Core biological role in mouse: epithelial development, homeostasis, and repair

3.2 Tissue expression/localization highlights in mouse

3.3 Skin/epidermal barrier and inflammation

3.4 Lung development

3.5 Kidney collecting duct physiology

3.6 Additional in vivo roles

4) Recent developments (prioritizing 2023–2024)

4.1 Nanoscale gating of ligand binding by tetraspanin nanodomains (2023)

4.2 Local lipid (PIP2) nanodomains regulate EGFR activation state (2024)

4.3 Endosomal sorting/degradation regulation as a determinant of signaling duration (2023–2024)

4.4 Ligand-free kinase-active oligomers in EGFR-mutant cancer (2024)

5) Current applications and real-world implementations

5.1 Therapeutics: EGFR inhibitors and resistance as a clinical driver

5.2 Diagnostics/imaging: EGFR conformation and mutation status

5.3 Organoids and mouse models as implementation platforms

6) Expert synthesis (interpretive analysis grounded in cited sources)

6.1 Primary functional role statement for annotation

6.2 Subcellular location statement for annotation

7) Visual evidence from authoritative source

8) Summary table (quick reference)

Key references with URLs (publication dates)

Citations

📚 Additional Documentation

Bioreason Rl Predictions

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Bioreason Rl Review

BioReason-Pro RL Review: Egfr (mouse)

Functional Summary Review

Notes on thinking trace

📄 View Raw YAML