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.
| 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 Ξ³-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-ductβspecific 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 PI3KβAKT. |
| 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 Ξ³-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 Ξ³-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 Ξ³-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 Ξ³-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 PI3KβAKT. |
| 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-ductβspecific 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 PI3KβAKT. |
| 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 Ξ³-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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT. |
| 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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-ductβspecific 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 Ξ³-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 PI3KβAKT. |
| 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 Ξ³-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 Ξ³-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 Ξ³-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 PI3KβAKT. |
| 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-ductβspecific 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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-ductβspecific 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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-ductβspecific 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-ductβspecific 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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-ductβspecific 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-ductβspecific 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 Ξ³-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 Ξ³-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 Ξ³-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 Ξ³-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 Ξ³-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 Ξ³-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 Ξ³-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 Ξ³-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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 Ξ³-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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 Ξ³-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 Ξ³-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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 Ξ³-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 Ξ³-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 Ξ³-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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 Ξ³-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 Ξ³-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 Ξ³-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 Ξ³-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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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-ductβspecific 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 Ξ³-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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT. |
| 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 PI3KβAKT. |
| 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 Ξ³-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 PI3KβAKT. |
| 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 PI3KβAKT. |
| 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 PI3KβAKT for anti-apoptotic survival and EGFRβMEKβERK 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 Ξ³-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**. |
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