Pro-epidermal growth factor is a membrane-anchored precursor that is processed to epidermal growth factor, a secreted EGFR ligand that stimulates epithelial and epidermal cell proliferation and activates EGFR-dependent MAPK, PI3K-AKT, and related signaling cascades.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0043410 positive regulation of MAPK cascade | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation. Reason: Receptor-mediated MAPK activation, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The pro-EGF precursor is a single-pass type I plasma-membrane protein, and membrane-anchored pro-EGF can signal juxtacrine; an accurate, evidence-backed localization for the gene product. Reason: Precursor is a type I plasma-membrane protein. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md Mouse **prepro‑EGF** is a **large type I transmembrane glycoprotein** (~**1217 amino acids**, ~133 kDa predicted core) with an N‑terminal signal peptide, a large extracellular region containing multiple cysteine-rich **EGF-like repeats**, a single transmembrane helix near the C-terminus, and a short cytoplasmic tail. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0008083 growth factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Mature EGF is a secreted growth factor that drives proliferation/differentiation of epidermal and epithelial tissues; this is a defining core molecular function of the gene product. Reason: Core ligand MF: EGF is the prototypical growth factor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0005154 epidermal growth factor receptor binding | IEA GO_REF:0000117 | ACCEPT | Summary: EGF binds EGFR/ErbB1 directly as a high-affinity (Kd 0.1-1 nM) agonist, the specific receptor-binding event underlying all EGF signaling; the single most informative MF term for this ligand. Reason: Core, specific receptor-binding MF for the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md classifying EGF among high-affinity ligands (apparent **Kd 0.1–1 nM**) |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Several EGF-like repeats in the precursor are calcium-binding (InterPro EGF-Ca domains), a structural property of the precursor; not the secreted ligand's core EGFR-agonist function. Reason: Structural Ca-binding of precursor EGF-Ca domains. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF-like_Ca-bd_dom. (IPR001881) |
| GO:0008083 growth factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Mature EGF is a secreted growth factor that drives proliferation/differentiation of epidermal and epithelial tissues; this is a defining core molecular function of the gene product. Reason: Core ligand MF: EGF is the prototypical growth factor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0010604 positive regulation of macromolecule metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Generic high-level metabolic-regulation term covered by more specific transcription/biosynthesis annotations; uninformative as standalone. Reason: Over-broad metabolic-regulation parent. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0016020 membrane | IEA GO_REF:0000044 | MODIFY | Summary: Bare 'membrane' under-specifies; pro-EGF is a type I plasma-membrane protein, so plasma membrane is the correct specific cellular component. Reason: Generic CC; precursor is plasma-membrane anchored. Proposed replacements: plasma membrane Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md Mouse **prepro‑EGF** is a **large type I transmembrane glycoprotein** (~**1217 amino acids**, ~133 kDa predicted core) with an N‑terminal signal peptide, a large extracellular region containing multiple cysteine-rich **EGF-like repeats**, a single transmembrane helix near the C-terminus, and a short cytoplasmic tail. |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Extremely broad developmental grouping term added by electronic inference; EGF's developmental roles are better captured by specific tissue terms, so this high-level term is uninformative. Reason: Over-broad parent developmental term. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md loss of a single ligand such as EGF can be phenotypically mild because other EGFR ligands provide compensatory signaling; stronger phenotypes emerge under combinatorial ligand loss or receptor perturbation. |
| GO:0048731 system development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Very high-level developmental term with little specificity for a single redundant EGFR ligand; over-annotation. Reason: Over-broad developmental grouping term. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md loss of a single ligand such as EGF can be phenotypically mild because other EGFR ligands provide compensatory signaling; stronger phenotypes emerge under combinatorial ligand loss or receptor perturbation. |
| GO:0051049 regulation of transport | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Generic high-level transport-regulation term; specific trafficking/ion annotations already capture the meaningful biology, so this parent is over-annotated. Reason: Over-broad transport-regulation parent. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. |
| GO:0071944 cell periphery | IEA GO_REF:0000117 | MODIFY | Summary: The precursor is a single-pass type I membrane protein; 'cell periphery' is uninformatively broad. The specific plasma-membrane location is curated and preferable. Reason: Too generic; specific plasma membrane known. Proposed replacements: plasma membrane Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md Mouse **prepro‑EGF** is a **large type I transmembrane glycoprotein** (~**1217 amino acids**, ~133 kDa predicted core) with an N‑terminal signal peptide, a large extracellular region containing multiple cysteine-rich **EGF-like repeats**, a single transmembrane helix near the C-terminus, and a short cytoplasmic tail. |
| GO:0080090 regulation of primary metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Very broad metabolic-regulation grouping term added electronically; provides no specific functional insight for EGF. Reason: Over-broad metabolic-regulation parent. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0001525 angiogenesis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF can contribute to angiogenesis through endothelial proliferation/migration, but this is a multicellular developmental outcome downstream of receptor signaling, not core ligand function. Reason: Developmental angiogenesis, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0001938 positive regulation of endothelial cell proliferation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF/EGFR signaling can promote endothelial proliferation in angiogenic contexts; a downstream tissue-specific output, non-core. Reason: Endothelial proliferation, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0002092 positive regulation of receptor internalization | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF binding triggers EGFR endocytosis/internalization for signal attenuation; a downstream trafficking consequence of ligand engagement, non-core MF. Reason: Ligand-induced receptor endocytosis, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. |
| GO:0005085 guanyl-nucleotide exchange factor activity | ISO GO_REF:0000119 | REMOVE | Summary: EGF is a secreted ligand, not a GEF; it has no nucleotide-exchange catalytic activity. GEF activity belongs to downstream intracellular components (e.g., SOS), not the ligand. Likely erroneous electronic/ortholog transfer. Reason: Ligand is not a GEF; contradicted by biology. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)** |
| GO:0007173 epidermal growth factor receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0008083 growth factor activity | ISO GO_REF:0000119 | ACCEPT | Summary: Mature EGF is a secreted growth factor that drives proliferation/differentiation of epidermal and epithelial tissues; this is a defining core molecular function of the gene product. Reason: Core ligand MF: EGF is the prototypical growth factor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0008284 positive regulation of cell population proliferation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0010595 positive regulation of endothelial cell migration | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF/EGFR signaling can promote endothelial migration in angiogenic/wound contexts; tissue-specific downstream effect, non-core. Reason: Endothelial migration, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF stimulation alters expression of many genes via EGFR-driven cascades; a generic downstream output retained as non-core. Reason: Generic downstream gene-expression change. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0010800 positive regulation of peptidyl-threonine phosphorylation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF-driven kinase cascades (e.g., MAPK) increase threonine phosphorylation of substrates; a downstream signaling consequence, non-core for the ligand. Reason: Downstream Thr-phospho via cascade, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0030335 positive regulation of cell migration | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF promotes cell motility/migration via EGFR (e.g., epithelial wound repair); a pleiotropic downstream output rather than core ligand MF. Reason: Pro-migratory output, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md in vivo, EREG-deficient ERK-biosensor mice show impaired ERK wave propagation and cell migration during skin wound repair. |
| GO:0042327 positive regulation of phosphorylation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF broadly increases protein phosphorylation through EGFR-initiated cascades; a generic downstream regulatory effect, retained as non-core. Reason: Generic downstream phosphorylation increase. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0043410 positive regulation of MAPK cascade | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation. Reason: Receptor-mediated MAPK activation, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0045840 positive regulation of mitotic nuclear division | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: As a mitogen, EGF promotes cell-cycle progression and mitosis downstream of EGFR; a pleiotropic consequence of receptor activation, non-core. Reason: Mitogenic output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF-induced signaling activates transcription factors and gene programs downstream of EGFR; a far-downstream nuclear consequence, non-core for the secreted ligand. Reason: Downstream transcriptional activation, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0051048 negative regulation of secretion | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF can modulate secretory processes downstream of receptor signaling; a pleiotropic physiological effect, non-core. Reason: Secretion modulation, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: PI3K/AKT activation is a canonical EGFR-downstream branch stimulated by EGF; downstream regulatory effect rather than core ligand activity. Reason: PI3K/AKT branch downstream of EGFR. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0070062 extracellular exosome | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF immunoreactive material can be recovered in extracellular vesicle/exosome fractions, but this is a secondary secretory route rather than the defining site where the ligand engages EGFR. Reason: Secondary secretory compartment, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md membrane-anchored ligand reservoir |
| GO:0070371 ERK1 and ERK2 cascade | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: ERK1/2 activation is a canonical cascade triggered by activated EGFR; it is a downstream consequence of EGF binding rather than an activity of the ligand itself. Reason: Downstream MAPK cascade, receptor-driven. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF/EGFR signaling can cross-talk with and potentiate canonical Wnt signaling, but this is an indirect pleiotropic effect, not a core ligand function. Reason: Cross-talk effect on Wnt, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0090279 regulation of calcium ion import | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF stimulation raises intracellular Ca2+ and, in distal nephron, EGF/EGFR engagement regulates ion (Mg2+/Ca2+) channel activity; a documented but tissue-specific downstream physiological role, non-core. Reason: Renal/cellular Ca ion-handling, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md Given the localization of Egf mRNA/proEGF to distal nephron segments (distal convoluted tubule; apical membrane association) and the observation of limited mature EGF release in kidney, one interpretation advanced in the early mouse precursor study is that unprocessed membrane proEGF could support specialized functions in distal tubular physiology, where Na+/H+ exchange is prominent and growth factor signaling can regulate this antiporter. |
| GO:1900127 positive regulation of hyaluronan biosynthetic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF/EGFR signaling can upregulate hyaluronan synthesis; a specific downstream metabolic output, non-core for the ligand. Reason: Hyaluronan synthesis upregulation, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:1902966 positive regulation of protein localization to early endosome | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Following EGF binding, internalized EGFR traffics to early endosomes; a downstream trafficking event consequent to receptor activation, non-core. Reason: Endosomal receptor trafficking, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. |
| GO:1905278 positive regulation of epithelial tube formation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGFR-ligand signaling supports epithelial tubulogenesis/branching; a developmental morphogenetic output downstream of the receptor, non-core. Reason: Epithelial tubulogenesis, developmental output. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:2000008 regulation of protein localization to cell surface | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: EGF signaling modulates cell-surface protein localization (e.g., receptor/transporter trafficking); a downstream regulatory effect, non-core. Reason: Surface-localization regulation, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. |
| GO:0001525 angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF can contribute to angiogenesis through endothelial proliferation/migration, but this is a multicellular developmental outcome downstream of receptor signaling, not core ligand function. Reason: Developmental angiogenesis, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0001938 positive regulation of endothelial cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF/EGFR signaling can promote endothelial proliferation in angiogenic contexts; a downstream tissue-specific output, non-core. Reason: Endothelial proliferation, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0002092 positive regulation of receptor internalization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF binding triggers EGFR endocytosis/internalization for signal attenuation; a downstream trafficking consequence of ligand engagement, non-core MF. Reason: Ligand-induced receptor endocytosis, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. |
| GO:0005085 guanyl-nucleotide exchange factor activity | IEA GO_REF:0000107 | REMOVE | Summary: EGF is a secreted ligand, not a GEF; it has no nucleotide-exchange catalytic activity. GEF activity belongs to downstream intracellular components (e.g., SOS), not the ligand. Likely erroneous electronic/ortholog transfer. Reason: Ligand is not a GEF; contradicted by biology. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)** |
| GO:0005615 extracellular space | IEA GO_REF:0000120 | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0010595 positive regulation of endothelial cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF/EGFR signaling can promote endothelial migration in angiogenic/wound contexts; tissue-specific downstream effect, non-core. Reason: Endothelial migration, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF stimulation alters expression of many genes via EGFR-driven cascades; a generic downstream output retained as non-core. Reason: Generic downstream gene-expression change. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0030297 transmembrane receptor protein tyrosine kinase activator activity | IEA GO_REF:0000107 | ACCEPT | Summary: By binding EGFR (a receptor tyrosine kinase) and promoting its dimerization, EGF activates the receptor's intrinsic tyrosine kinase; an accurate, specific agonist MF for this ligand. Reason: Core: ligand activates the RTK EGFR. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0030335 positive regulation of cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF promotes cell motility/migration via EGFR (e.g., epithelial wound repair); a pleiotropic downstream output rather than core ligand MF. Reason: Pro-migratory output, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md in vivo, EREG-deficient ERK-biosensor mice show impaired ERK wave propagation and cell migration during skin wound repair. |
| GO:0038134 ERBB2-EGFR signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF can drive EGFR-ErbB2 heterodimer signaling, but heterodimer-specific transduction is a receptor-level event downstream of ligand binding; relevant but not the ligand's core function. Reason: Receptor heterodimer signaling, downstream of ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0042327 positive regulation of phosphorylation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF broadly increases protein phosphorylation through EGFR-initiated cascades; a generic downstream regulatory effect, retained as non-core. Reason: Generic downstream phosphorylation increase. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0043410 positive regulation of MAPK cascade | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation. Reason: Receptor-mediated MAPK activation, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0045840 positive regulation of mitotic nuclear division | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: As a mitogen, EGF promotes cell-cycle progression and mitosis downstream of EGFR; a pleiotropic consequence of receptor activation, non-core. Reason: Mitogenic output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF-induced signaling activates transcription factors and gene programs downstream of EGFR; a far-downstream nuclear consequence, non-core for the secreted ligand. Reason: Downstream transcriptional activation, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0048018 receptor ligand activity | IEA GO_REF:0000107 | ACCEPT | Summary: EGF acts as a diffusible/juxtacrine ligand that engages and activates its cognate receptor EGFR; correct core agonist MF, complementary to the specific EGFR-binding term. Reason: Core agonist ligand MF. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0051048 negative regulation of secretion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF can modulate secretory processes downstream of receptor signaling; a pleiotropic physiological effect, non-core. Reason: Secretion modulation, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PI3K/AKT activation is a canonical EGFR-downstream branch stimulated by EGF; downstream regulatory effect rather than core ligand activity. Reason: PI3K/AKT branch downstream of EGFR. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0070062 extracellular exosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF immunoreactive material can be recovered in extracellular vesicle/exosome fractions, but this is a secondary secretory route rather than the defining site where the ligand engages EGFR. Reason: Secondary secretory compartment, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md membrane-anchored ligand reservoir |
| GO:0070371 ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ERK1/2 activation is a canonical cascade triggered by activated EGFR; it is a downstream consequence of EGF binding rather than an activity of the ligand itself. Reason: Downstream MAPK cascade, receptor-driven. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF/EGFR signaling can cross-talk with and potentiate canonical Wnt signaling, but this is an indirect pleiotropic effect, not a core ligand function. Reason: Cross-talk effect on Wnt, pleiotropic. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0090279 regulation of calcium ion import | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF stimulation raises intracellular Ca2+ and, in distal nephron, EGF/EGFR engagement regulates ion (Mg2+/Ca2+) channel activity; a documented but tissue-specific downstream physiological role, non-core. Reason: Renal/cellular Ca ion-handling, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md Given the localization of Egf mRNA/proEGF to distal nephron segments (distal convoluted tubule; apical membrane association) and the observation of limited mature EGF release in kidney, one interpretation advanced in the early mouse precursor study is that unprocessed membrane proEGF could support specialized functions in distal tubular physiology, where Na+/H+ exchange is prominent and growth factor signaling can regulate this antiporter. |
| GO:1900127 positive regulation of hyaluronan biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF/EGFR signaling can upregulate hyaluronan synthesis; a specific downstream metabolic output, non-core for the ligand. Reason: Hyaluronan synthesis upregulation, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:1902966 positive regulation of protein localization to early endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Following EGF binding, internalized EGFR traffics to early endosomes; a downstream trafficking event consequent to receptor activation, non-core. Reason: Endosomal receptor trafficking, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. |
| GO:1905278 positive regulation of epithelial tube formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGFR-ligand signaling supports epithelial tubulogenesis/branching; a developmental morphogenetic output downstream of the receptor, non-core. Reason: Epithelial tubulogenesis, developmental output. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:2000008 regulation of protein localization to cell surface | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF signaling modulates cell-surface protein localization (e.g., receptor/transporter trafficking); a downstream regulatory effect, non-core. Reason: Surface-localization regulation, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. |
| GO:0005615 extracellular space | ISO GO_REF:0000119 | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0005154 epidermal growth factor receptor binding | ISO GO_REF:0000096 | ACCEPT | Summary: EGF binds EGFR/ErbB1 directly as a high-affinity (Kd 0.1-1 nM) agonist, the specific receptor-binding event underlying all EGF signaling; the single most informative MF term for this ligand. Reason: Core, specific receptor-binding MF for the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md classifying EGF among high-affinity ligands (apparent **Kd 0.1–1 nM**) |
| GO:0005615 extracellular space | ISO GO_REF:0000096 | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0007173 epidermal growth factor receptor signaling pathway | ISO GO_REF:0000096 | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0048146 positive regulation of fibroblast proliferation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: EGF stimulates proliferation of some fibroblasts in culture; a tissue-specific downstream proliferative effect, non-core. Reason: Fibroblast proliferation, tissue-specific output. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: EGF positively regulates the ERK1/2 cascade indirectly via EGFR activation; correct as a pleiotropic regulatory effect downstream of the receptor, not a core ligand MF. Reason: Positive ERK regulation via receptor, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:2000573 positive regulation of DNA biosynthetic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: As a mitogen, EGF promotes DNA replication during cell-cycle entry; a downstream proliferative consequence, non-core. Reason: DNA synthesis as mitogenic readout. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0030297 transmembrane receptor protein tyrosine kinase activator activity | ISO GO_REF:0000119 | ACCEPT | Summary: By binding EGFR (a receptor tyrosine kinase) and promoting its dimerization, EGF activates the receptor's intrinsic tyrosine kinase; an accurate, specific agonist MF for this ligand. Reason: Core: ligand activates the RTK EGFR. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0008284 positive regulation of cell population proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0043410 positive regulation of MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation. Reason: Receptor-mediated MAPK activation, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0048018 receptor ligand activity | IDA PMID:11823423 A mutant EGF-receptor defective in ubiquitylation and endocy... | ACCEPT | Summary: EGF acts as a diffusible/juxtacrine ligand that engages and activates its cognate receptor EGFR; correct core agonist MF, complementary to the specific EGFR-binding term. Reason: Core agonist ligand MF. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0048018 receptor ligand activity | IDA PMID:14627991 Serine mutations that abrogate ligand-induced ubiquitination... | ACCEPT | Summary: EGF acts as a diffusible/juxtacrine ligand that engages and activates its cognate receptor EGFR; correct core agonist MF, complementary to the specific EGFR-binding term. Reason: Core agonist ligand MF. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0005615 extracellular space | IDA PMID:12761849 EGF-stimulated signaling by means of PI3K, PLCgamma1, and PK... | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:12761849 EGF-stimulated signaling by means of PI3K, PLCgamma1, and PK... | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:9529375 Epidermal growth factor signaling and mitogenesis in Plcg1 n... | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0048018 receptor ligand activity | IDA PMID:12761849 EGF-stimulated signaling by means of PI3K, PLCgamma1, and PK... | ACCEPT | Summary: EGF acts as a diffusible/juxtacrine ligand that engages and activates its cognate receptor EGFR; correct core agonist MF, complementary to the specific EGFR-binding term. Reason: Core agonist ligand MF. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0048018 receptor ligand activity | IDA PMID:9529375 Epidermal growth factor signaling and mitogenesis in Plcg1 n... | ACCEPT | Summary: EGF acts as a diffusible/juxtacrine ligand that engages and activates its cognate receptor EGFR; correct core agonist MF, complementary to the specific EGFR-binding term. Reason: Core agonist ligand MF. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0005615 extracellular space | ISO PMID:11336639 Heterodimerization of the epidermal-growth-factor (EGF) rece... | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0005615 extracellular space | IDA PMID:22822073 Quantitation of the effect of ErbB2 on epidermal growth fact... | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0005615 extracellular space | IDA PMID:6248866 Detection of epidermal growth factor-urogastrone and its rec... | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0005615 extracellular space | IDA PMID:7752576 Tyrosine kinase activity of the EGF receptor in murine metan... | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0038134 ERBB2-EGFR signaling pathway | ISO PMID:11336639 Heterodimerization of the epidermal-growth-factor (EGF) rece... | KEEP AS NON CORE | Summary: EGF can drive EGFR-ErbB2 heterodimer signaling, but heterodimer-specific transduction is a receptor-level event downstream of ligand binding; relevant but not the ligand's core function. Reason: Receptor heterodimer signaling, downstream of ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0038134 ERBB2-EGFR signaling pathway | IDA PMID:22822073 Quantitation of the effect of ErbB2 on epidermal growth fact... | KEEP AS NON CORE | Summary: EGF can drive EGFR-ErbB2 heterodimer signaling, but heterodimer-specific transduction is a receptor-level event downstream of ligand binding; relevant but not the ligand's core function. Reason: Receptor heterodimer signaling, downstream of ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0048018 receptor ligand activity | ISO PMID:11336639 Heterodimerization of the epidermal-growth-factor (EGF) rece... | ACCEPT | Summary: EGF acts as a diffusible/juxtacrine ligand that engages and activates its cognate receptor EGFR; correct core agonist MF, complementary to the specific EGFR-binding term. Reason: Core agonist ligand MF. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0048018 receptor ligand activity | IDA PMID:22822073 Quantitation of the effect of ErbB2 on epidermal growth fact... | ACCEPT | Summary: EGF acts as a diffusible/juxtacrine ligand that engages and activates its cognate receptor EGFR; correct core agonist MF, complementary to the specific EGFR-binding term. Reason: Core agonist ligand MF. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:6248866 Detection of epidermal growth factor-urogastrone and its rec... | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:7752576 Tyrosine kinase activity of the EGF receptor in murine metan... | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0048018 receptor ligand activity | IDA PMID:6248866 Detection of epidermal growth factor-urogastrone and its rec... | ACCEPT | Summary: EGF acts as a diffusible/juxtacrine ligand that engages and activates its cognate receptor EGFR; correct core agonist MF, complementary to the specific EGFR-binding term. Reason: Core agonist ligand MF. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0048018 receptor ligand activity | IDA PMID:7752576 Tyrosine kinase activity of the EGF receptor in murine metan... | ACCEPT | Summary: EGF acts as a diffusible/juxtacrine ligand that engages and activates its cognate receptor EGFR; correct core agonist MF, complementary to the specific EGFR-binding term. Reason: Core agonist ligand MF. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0043410 positive regulation of MAPK cascade | IDA PMID:16339969 Efficient suppression of FGF-2-induced ERK activation by the... | KEEP AS NON CORE | Summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation. Reason: Receptor-mediated MAPK activation, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0043410 positive regulation of MAPK cascade | IDA PMID:9030684 Mutation in Sos1 dominantly enhances a weak allele of the EG... | KEEP AS NON CORE | Summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation. Reason: Receptor-mediated MAPK activation, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:8702723 The epidermal growth factor receptor couples transforming gr... | KEEP AS NON CORE | Summary: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0005154 epidermal growth factor receptor binding | IDA PMID:7678348 Expression of the epidermal growth factor receptor gene is r... | ACCEPT | Summary: EGF binds EGFR/ErbB1 directly as a high-affinity (Kd 0.1-1 nM) agonist, the specific receptor-binding event underlying all EGF signaling; the single most informative MF term for this ligand. Reason: Core, specific receptor-binding MF for the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md classifying EGF among high-affinity ligands (apparent **Kd 0.1–1 nM**) |
| GO:0061098 positive regulation of protein tyrosine kinase activity | IDA PMID:7678348 Expression of the epidermal growth factor receptor gene is r... | KEEP AS NON CORE | Summary: EGF activates the EGFR tyrosine kinase (and downstream kinases); captured more specifically by the RTK-activator MF, this BP term is a valid but non-core downstream effect. Reason: Activates kinases downstream; non-core BP. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation | IDA PMID:21186272 Activation of the neuregulin/ErbB system during physiologica... | KEEP AS NON CORE | Summary: EGF increases cellular tyrosine phosphorylation by activating EGFR's kinase; correct as a positive-regulation process attributable to the ligand, but downstream and non-core. Reason: Regulatory (not catalytic) tyrosine-phospho effect. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0043388 positive regulation of DNA binding | IDA PMID:15156153 Hes binding to STAT3 mediates crosstalk between Notch and JA... | KEEP AS NON CORE | Summary: EGF signaling increases DNA-binding activity of downstream transcription factors; a distal nuclear regulatory consequence of receptor activation, non-core. Reason: Downstream TF DNA-binding effect. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0046425 regulation of receptor signaling pathway via JAK-STAT | IDA PMID:15156153 Hes binding to STAT3 mediates crosstalk between Notch and JA... | KEEP AS NON CORE | Summary: EGF/EGFR signaling engages JAK-STAT (e.g., Stat5a in lactation, Stat1 in hepatocytes); a downstream regulatory cross-talk consequence of receptor activation rather than core ligand MF. Reason: JAK-STAT cross-talk downstream of EGFR. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md Stat5a phosphorylation was conspicuously decreased in AR-deficient contexts (especially double/triple nulls), linking EGFR-ligand signaling to lactation-associated STAT activation. |
| GO:0090370 negative regulation of cholesterol efflux | IDA PMID:20037141 Inhibition of ERK1/2 and activation of liver X receptor syne... | KEEP AS NON CORE | Summary: An IDA-supported specific metabolic effect of EGF signaling on cholesterol efflux; a narrow downstream physiological output, non-core for the ligand. Reason: Specific cholesterol-efflux effect, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:2000060 positive regulation of ubiquitin-dependent protein catabolic process | IDA PMID:20208556 Presenilin modulates EGFR signaling and cell transformation ... | KEEP AS NON CORE | Summary: EGF binding leads to ubiquitination and lysosomal/proteasomal degradation of activated EGFR; an IDA-supported downstream catabolic consequence, non-core. Reason: Ligand-triggered receptor degradation, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. |
| GO:0051223 regulation of protein transport | ISO PMID:19723622 Activator of G protein signaling 8 (AGS8) is required for hy... | KEEP AS NON CORE | Summary: EGF-initiated signaling regulates intracellular protein transport/trafficking; a pleiotropic downstream effect, non-core for the ligand. Reason: Protein-transport regulation, downstream. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. |
| GO:0005515 protein binding | IPI PMID:17626015 SGIP1alpha is an endocytic protein that directly interacts w... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' is uninformative; the specific and curated 'epidermal growth factor receptor binding' captures the meaningful interaction. Always over-annotated. Reason: Generic MF superseded by EGFR-binding term. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)** |
| GO:0005886 plasma membrane | IDA PMID:17626015 SGIP1alpha is an endocytic protein that directly interacts w... | ACCEPT | Summary: The pro-EGF precursor is a single-pass type I plasma-membrane protein, and membrane-anchored pro-EGF can signal juxtacrine; an accurate, evidence-backed localization for the gene product. Reason: Precursor is a type I plasma-membrane protein. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md Mouse **prepro‑EGF** is a **large type I transmembrane glycoprotein** (~**1217 amino acids**, ~133 kDa predicted core) with an N‑terminal signal peptide, a large extracellular region containing multiple cysteine-rich **EGF-like repeats**, a single transmembrane helix near the C-terminus, and a short cytoplasmic tail. |
| GO:0008083 growth factor activity | ISO GO_REF:0000008 | ACCEPT | Summary: Mature EGF is a secreted growth factor that drives proliferation/differentiation of epidermal and epithelial tissues; this is a defining core molecular function of the gene product. Reason: Core ligand MF: EGF is the prototypical growth factor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0008284 positive regulation of cell population proliferation | ISO GO_REF:0000008 | KEEP AS NON CORE | Summary: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0005154 epidermal growth factor receptor binding | IDA PMID:6315706 Epidermal growth factor-like transforming growth factor. II.... | ACCEPT | Summary: EGF binds EGFR/ErbB1 directly as a high-affinity (Kd 0.1-1 nM) agonist, the specific receptor-binding event underlying all EGF signaling; the single most informative MF term for this ligand. Reason: Core, specific receptor-binding MF for the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md classifying EGF among high-affinity ligands (apparent **Kd 0.1–1 nM**) |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:6315706 Epidermal growth factor-like transforming growth factor. II.... | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0060749 mammary gland alveolus development | IGI PMID:10331984 Targeted inactivation of the EGF and amphiregulin genes reve... | KEEP AS NON CORE | Summary: Combinatorial Egf/Areg/Tgfa knockouts show EGF supports mammary alveolar differentiation/lactogenesis; an IGI-supported tissue-specific developmental role, non-core for the ligand's molecular function. Reason: Mammary alveolar development, genetic support. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md In the Egf/Areg/Tgfa combinatorial knockout framework, amphiregulin is essential for pubertal ductal outgrowth, while EGF and TGFα support lactogenesis. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-179883 | ACCEPT | Summary: The processed mature EGF peptide is released and acts in the extracellular region; secreted localization is core to a diffusible growth-factor ligand. Reason: Core: secreted ligand acts extracellularly. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-179883 | ACCEPT | Summary: The pro-EGF precursor is a single-pass type I plasma-membrane protein, and membrane-anchored pro-EGF can signal juxtacrine; an accurate, evidence-backed localization for the gene product. Reason: Precursor is a type I plasma-membrane protein. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md Mouse **prepro‑EGF** is a **large type I transmembrane glycoprotein** (~**1217 amino acids**, ~133 kDa predicted core) with an N‑terminal signal peptide, a large extracellular region containing multiple cysteine-rich **EGF-like repeats**, a single transmembrane helix near the C-terminus, and a short cytoplasmic tail. |
| GO:0005615 extracellular space | IDA PMID:7641815 Altering the expression of cell surface beta 1,4-galactosylt... | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IGI PMID:7641815 Altering the expression of cell surface beta 1,4-galactosylt... | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| 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: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0021940 positive regulation of cerebellar granule cell precursor proliferation | IDA PMID:10027293 Control of neuronal precursor proliferation in the cerebellu... | KEEP AS NON CORE | Summary: A specific neural proliferative effect attributable to EGFR-ligand signaling; biologically plausible but a narrow pleiotropic downstream output, retained as non-core rather than removed. Reason: Narrow neural proliferative output, non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0008284 positive regulation of cell population proliferation | IGI PMID:15051883 Neuropoietin, a new IL-6-related cytokine signaling through ... | KEEP AS NON CORE | Summary: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0048754 branching morphogenesis of an epithelial tube | IDA PMID:15831470 Integrin-linked kinase mediates bone morphogenetic protein 7... | KEEP AS NON CORE | Summary: EGF contributes to epithelial branching morphogenesis (e.g., mammary/salivary) via EGFR; an IDA-supported developmental role best treated as a pleiotropic downstream process, not removed. Reason: Branching morphogenesis, developmental; keep non-core. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md In the Egf/Areg/Tgfa combinatorial knockout framework, amphiregulin is essential for pubertal ductal outgrowth, while EGF and TGFα support lactogenesis. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:15695332 Suppressor of cytokine signaling (SOCS)-5 is a potential neg... | ACCEPT | Summary: EGF is the canonical initiating ligand of the EGFR signaling pathway; the gene's participation in this pathway is its central biological role and is strongly experimentally supported. Reason: Core pathway initiated by the ligand. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md EGF binding activates EGFR tyrosine kinase and triggers multiple downstream cascades including **Ras/Raf/MEK/ERK**, **PI3K/AKT/mTOR**, **JAK/STAT**, and **PLC/PKC**, shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:15695332 Suppressor of cytokine signaling (SOCS)-5 is a potential neg... | KEEP AS NON CORE | Summary: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| 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: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0008284 positive regulation of cell population proliferation | IGI PMID:15509736 Fibroblast growth factor receptor signaling promotes radial ... | KEEP AS NON CORE | Summary: Stimulating proliferation is a hallmark biological output of EGF, but it is a pleiotropic downstream consequence of EGFR activation rather than the ligand's core molecular function. Reason: Proliferative output downstream of receptor. Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**, triggering receptor dimerization and activation of EGFR’s intrinsic tyrosine kinase, thereby controlling cellular proliferation, differentiation, survival and motility—especially in epithelial contexts. |
| GO:0005615 extracellular space | IDA PMID:8240367 An inborn error in epidermal growth factor prohormone metabo... | ACCEPT | Summary: Mature EGF is shed from the membrane precursor into extracellular space (e.g., saliva, plasma ~1 ng/mL) where it reaches EGFR; well-supported core localization. Reason: Core secreted localization (IDA-supported). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. file:mouse/Egf/Egf-deep-research-falcon.md the **mature EGF ligand** is a **53-aa** (~**6–8 kDa**) segment located immediately N‑terminal to the transmembrane region that can be released by proteolysis. |
| GO:0018108 peptidyl-tyrosine phosphorylation | IDA PMID:14561752 N-acetylglucosaminyltransferase V expression levels regulate... | MARK AS OVER ANNOTATED | Summary: This catalytic process is carried out by the EGF receptor, not by the secreted EGF ligand; the IDA most likely reflects EGF-stimulated phosphorylation over-attributed to the ligand. Reason: Catalytic process belongs to the receptor; over-annotation of the ligand (downgraded from REMOVE as it carries IDA evidence). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. |
| GO:0050730 regulation of peptidyl-tyrosine phosphorylation | IDA PMID:11940581 Protein kinase C-alpha and protein kinase C-epsilon are requ... | KEEP AS NON CORE | Summary: By binding and activating EGFR, EGF positively regulates downstream peptidyl-tyrosine phosphorylation; a real regulatory effect of the ligand. Reason: Downstream regulatory effect of ligand-receptor engagement; non-core (experimental IDA retained). Supporting Evidence: UniProt:P01132 FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. |
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