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.
|
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The target gene is Egf from Mus musculus (mouse), encoding pro-epidermal growth factor (prepro‑EGF/proEGF), a membrane-anchored precursor that is proteolytically processed to generate mature epidermal growth factor (EGF), the canonical ligand for EGFR/ErbB1. This identity is explicitly described in mouse primary studies that sequenced the 1217-aa precursor and examined its tissue distribution and processing, and in an authoritative review that synthesizes gene organization, precursor structure and physiology. (scott1985thestructureand pages 1-4, zeng2014epidermalgrowthfactor pages 2-4)
| Category | Key points | Best supporting sources |
|---|---|---|
| Identity | Target verified as Mus musculus Egf, UniProt P01132, encoding pro-epidermal growth factor / prepro-EGF, the precursor of mature EGF. Literature distinguishes the mouse membrane-anchored precursor from mature soluble EGF. | (zeng2014epidermalgrowthfactor pages 2-2, zeng2014epidermalgrowthfactor pages 2-4, scott1985thestructureand pages 1-4) |
| Protein architecture | Mouse prepro-EGF is a large type I transmembrane glycoprotein of about 1217 aa with an N-terminal signal peptide, multiple EGF-like repeats in the extracellular region, the 53-aa mature EGF segment near the C-terminus, a single transmembrane domain, and a short cytoplasmic tail; potential N-glycosylation and multiple dibasic cleavage sites are present. A figure-based domain map shows seven EGF-like peptides, the mature EGF moiety, glycosylation sites, and candidate processing sites. | (zeng2014epidermalgrowthfactor pages 2-2, scott1985thestructureand pages 4-7, scott1985thestructureand pages 1-4, scott1985thestructureand media d2d35de8) |
| Processing/biogenesis | Mature EGF is produced by proteolytic cleavage/shedding from membrane pro-EGF. Processing is tissue-specific: submaxillary gland efficiently processes/stores mature low-MW EGF in secretory granules, whereas kidney contains predominantly unprocessed high-MW precursor and urinary high-MW EGF species, implying partial distal proteolysis rather than complete maturation in situ. In platelets, cleavage between the EGF domain and TM segment can release biologically active HMW-EGF; ADAMDEC1 was shown to mediate this in a platelet context. | (zeng2014epidermalgrowthfactor pages 2-2, chen2017thesolubleprotease pages 1-2, scott1985thestructureand pages 4-7, lakshmanan1990identificationofproepidermal pages 1-3) |
| Localization/expression | Highest expression is reported in submaxillary/salivary gland and kidney. In kidney, Egf mRNA/protein localize mainly to distal convoluted tubules and thick ascending limb/apical tubular membranes; expression is also reported in tooth buds and lower levels in mammary gland, pancreas, intestine, ovary, spleen, lung, pituitary, and liver. | (zeng2014epidermalgrowthfactor pages 2-4, scott1985thestructureand pages 4-7, scott1985thestructureand pages 1-4, lakshmanan1990identificationofproepidermal pages 1-3) |
| Molecular function | The primary function is EGFR ligand activity: mature EGF, and in some contexts pro-EGF itself, binds EGFR/ErbB1, triggering receptor dimerization and tyrosine kinase activation to regulate cell proliferation, differentiation, survival, migration, and epithelial repair. Membrane-bound precursor may additionally support juxtacrine/paracrine signaling. | (zeng2014epidermalgrowthfactor pages 2-2, zeng2014epidermalgrowthfactor pages 2-4, fisher1990metabolismandeffects pages 2-3) |
| Pathways | Canonical downstream pathways include Ras/Raf/MEK/ERK, PI3K/AKT/mTOR, JAK/STAT, and PLC/PKC; older mechanistic work also links EGF signaling to Na+/H+ exchange, intracellular Ca2+ changes, and increased nutrient transport. | (zeng2014epidermalgrowthfactor pages 2-4, fisher1990metabolismandeffects pages 2-3) |
| Phenotypes/models | Egf knockout mice reportedly show no overt gross phenotype, consistent with redundancy among EGFR ligands. In contrast, transgenic EGF overexpression causes low birth weight/stunted growth and reproductive defects, supporting dosage-sensitive developmental roles. | (zeng2014epidermalgrowthfactor pages 2-4) |
| Quantitative data | Reported values include: mouse prepro-EGF 1217 aa; mature EGF 53 aa (~6 kDa); plasma EGF about 1 ng/mL; adult male submaxillary gland EGF about 1000 ng/mg wet tissue versus about 70 ng/mg in females; submaxillary gland:kidney protein ratio about 2000:1 despite only about 2:1 mRNA ratio; male:female submaxillary mRNA about 10:1; urinary pro-EGF species detected at about 165, 116, 97, 66, and 56 kDa. | (zeng2014epidermalgrowthfactor pages 2-2, scott1985thestructureand pages 4-7, lakshmanan1990identificationofproepidermal pages 1-3) |
| Notes/limitations | Direct recent (2023–2024) mouse Egf-specific primary literature is limited relative to the broader EGFR ligand field; many newer studies focus on EGFR or other ligands (e.g., HB-EGF, TGF-α). Some cleavage mechanisms are context-dependent, and evidence for specific sheddases of mouse renal/salivary pro-EGF remains less definitive than the general membrane-precursor model. | (zeng2014epidermalgrowthfactor pages 2-4, chen2017thesolubleprotease pages 1-2, scott1985thestructureand pages 4-7) |
Table: This table condenses the key functional-annotation findings for mouse Egf (UniProt P01132), covering identity, protein structure, processing, localization, signaling, phenotypes, and quantitative observations. It is useful as a citation-linked summary of the strongest evidence already gathered.
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. (scott1985thestructureand pages 1-4, zeng2014epidermalgrowthfactor pages 2-4)
A key concept is that EGF is not synthesized as a standalone secreted peptide, but as part of this precursor; 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. (zeng2014epidermalgrowthfactor pages 2-2, zeng2014epidermalgrowthfactor pages 2-4)
A figure from the original mouse precursor characterization visually maps: (i) multiple EGF-like peptides, (ii) the mature EGF domain, (iii) N‑glycosylation sites, (iv) dibasic candidate processing sites, and (v) the transmembrane anchor. (scott1985thestructureand media d2d35de8)
“Processing” refers to proteolytic cleavage of proEGF to release soluble EGF-containing ligands. In the mouse submaxillary gland, EGF is synthesized and processed and only the mature ~6 kDa EGF species is detected in secretory granules, consistent with regulated exocytotic release. (zeng2014epidermalgrowthfactor pages 2-2)
A second important concept is that processing is tissue- and context-dependent: kidney expresses high Egf mRNA but predominantly retains high-molecular-weight precursor forms, with little evidence of complete maturation to 6 kDa EGF in situ. (scott1985thestructureand pages 4-7, lakshmanan1990identificationofproepidermal pages 1-3)
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. (zeng2014epidermalgrowthfactor pages 2-4, fisher1990metabolismandeffects pages 2-3)
Mouse prepro‑EGF was deduced from cDNA as a 1217-aa precursor with a signal peptide, multiple EGF-like motifs, potential N-glycosylation sites, and a ~20-aa hydrophobic transmembrane segment near the C-terminus. (scott1985thestructureand pages 1-4, scott1985thestructureand pages 4-7)
Evidence from early mouse work supports a membrane-anchored precursor model, including the hydrophobic C-terminal segment that could span the plasma membrane and a basic C-terminus that could stabilize membrane association. (scott1985thestructureand pages 4-7)
In kidney, proEGF is reported to accumulate as prepro‑EGF associated with the apical membrane of epithelial cells; mature 6 kDa EGF is not readily detectable in kidney by immunostaining/biochemical assays in the reviewed and primary literature. (zeng2014epidermalgrowthfactor pages 2-4, lakshmanan1990identificationofproepidermal pages 1-3)
Mouse Egf mRNA is highest in submaxillary (salivary) gland and is also surprisingly high in the kidney. In situ hybridization localizes kidney Egf mRNA predominantly to the cortex and especially to distal convoluted tubules. (scott1985thestructureand pages 4-7)
The same mouse study reports additional expression (descending) in lactating mammary gland, pancreas, small intestine, ovary, spleen, lung, pituitary, and liver. (scott1985thestructureand pages 4-7)
A strong male-biased expression occurs in mouse submaxillary gland: the mRNA level is ~10:1 male:female in the classic dot-blot analysis, and adult male submaxillary gland contains far higher EGF protein than females (quantitatively summarized in the later review). (scott1985thestructureand pages 4-7, zeng2014epidermalgrowthfactor pages 2-2)
In secretory tissues such as the mouse submaxillary gland, EGF is synthesized and processed and stored in secretory granules; only the mature ~6 kDa EGF is detected in those granules and released via exocytosis. Adrenergic stimulation (e.g., phenylephrine or stress) can dramatically increase EGF levels in saliva and blood. (zeng2014epidermalgrowthfactor pages 2-2, zeng2014epidermalgrowthfactor pages 2-4)
Quantitatively, the review reports very high submaxillary gland EGF in adult male mice (~1000 ng/mg wet tissue) compared with females (~70 ng/mg), with plasma EGF around ~1 ng/mL and no sex difference in plasma. (zeng2014epidermalgrowthfactor pages 2-2)
Despite high kidney Egf mRNA, early experimental work found a striking discordance between mRNA and protein: the submaxillary:kidney EGF protein ratio ~2000:1 versus only ~2:1 at mRNA level, and metabolic labeling/immunoprecipitation showed kidney predominantly contains an ~130 kDa precursor with no clear evidence of mature EGF production under those conditions. (scott1985thestructureand pages 4-7)
Urine and kidney extracts contain high-molecular-weight EGF-immunoreactive species consistent with proEGF and partial proteolysis products. In adult mouse urine, immunoblotting detected a major proEGF band at ~165 kDa and additional EGF-containing species at ~116, 97, 66, and 56 kDa, while 6 kDa EGF was not detected by those assays. (lakshmanan1990identificationofproepidermal pages 1-3)
In a platelet system (human-focused but mechanistically informative for proEGF processing biology), proEGF was found on platelet membranes and converted to a soluble high-molecular-weight EGF by a single cleavage between the EGF domain and the transmembrane region, generating an EGFR-activating ligand; the study identified ADAMDEC1 as the soluble protease mediating this conversion in activated platelets. (chen2017thesolubleprotease pages 1-2)
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. (zeng2014epidermalgrowthfactor pages 2-4)
Mechanistic endocrine-review evidence also links EGF stimulation to early physiological outputs including activation of Na+/H+ exchange (alkalinization), increased intracellular Ca2+, and increased amino acid and glucose transport; receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis. (fisher1990metabolismandeffects pages 2-3)
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. (scott1985thestructureand pages 4-7)
Multiple sources report that Egf-null mice show no overt phenotype, consistent with compensatory signaling by other EGFR ligands. In a widely cited genetic study, targeted removal of EGF (with amphiregulin and TGFα combinations) produced animals that were generally viable and fertile, but revealed strong mammary phenotypes when amphiregulin was absent. (luetteke1999targetedinactivationof pages 1-2, sibilia2007theepidermalgrowth pages 2-4)
Molecular validation in the mammary-development study includes northern and western evidence that EGF transcript/protein products are absent from salivary gland and kidney (and mature ~6 kDa EGF not detected) in EGF-null animals, confirming true ligand loss. (luetteke1999targetedinactivationof pages 2-3)
In the Egf/Areg/Tgfa combinatorial knockout framework, amphiregulin is essential for pubertal ductal outgrowth, while EGF and TGFα support lactogenesis. Triple-null dams frequently failed to nurse effectively; triple-null glands had poorly organized/differentiated alveoli and reduced milk-gene expression, and Stat5a phosphorylation was conspicuously decreased in AR-deficient contexts (especially double/triple nulls), linking EGFR-ligand signaling to lactation-associated STAT activation. (luetteke1999targetedinactivationof pages 1-2, luetteke1999targetedinactivationof pages 6-7)
Transgenic mice widely expressing an engineered EGF precursor were “consistently born at half the normal weight” and reached almost 80% of normal weight as adults, with associated reductions in serum IGFBP-3 and changes in growth plate chondrocytes/osteoblast localization. (chan2000expressionofepidermal pages 1-2)
Direct 2023–2024 mouse studies focused specifically on Egf/proEGF (as opposed to EGFR signaling broadly or other ligands) are relatively sparse in the retrieved full texts; however, several 2024 studies provide updated mechanistic context for EGFR-ligand biology relevant to interpreting Egf function.
A 2024 preprint quantitatively differentiates EGFR ligands by binding affinity and shedding sensitivity, classifying EGF among high-affinity ligands (apparent Kd 0.1–1 nM) and noting that ADAM17-mediated shedding occurs for several ligands but not for EGF (nor BTC) in the cited probe-based shedding assays. The work links ADAM17-dependent ligand shedding to propagation of ERK activation waves during collective migration and reports that low-affinity ligands can act as long-range signal transmitters; in vivo, EREG-deficient ERK-biosensor mice show impaired ERK wave propagation and cell migration during skin wound repair. These results refine how different EGFR ligands (including EGF) may contribute to spatial signaling dynamics in tissues. (deguchi2024lowaffinityligandsof pages 1-4)
In a 2024 mouse study of seizure-induced hippocampal remodeling, EGFR signaling is shown to be a key driver of conversion of neural stem cells into reactive phenotypes, with EGFR inhibition by gefitinib preventing reactive NSC induction and preserving neurogenesis. Quantitatively, hippocampal ERK1/2 phosphorylation increased ~8-fold at 1.5 h post-kainic acid and remained ~10–20-fold elevated later; EGFR abundance increased and became significant at 72 h (~15-fold, P=0.043). Although the ligand emphasized is HB-EGF rather than EGF, the study exemplifies modern in vivo pharmacologic and signaling readouts used to interrogate EGFR-ligand axes in mouse biology. (pastoralonso2024hbegfactivatesegfr pages 1-2)
A 2024 meeting abstract reports that EGF signaling maintains hepatocyte ECM1 expression via STAT1 S727 phosphorylation and promoter binding, and that IFNγ/NRF2 disrupts this axis in chronic liver disease contexts. The excerpted material does not provide detailed quantitative measurements, so these conclusions should be treated as preliminary until full peer-reviewed data are available. (li2024egfstat1maintainedecm1expression pages 1-5)
Mouse genetics for pathway dissection. Egf null and combinatorial EGFR-ligand knockouts (e.g., Egf/Areg/Tgfa) are used to separate ligand-specific versus redundant functions in vivo, notably in mammary gland morphogenesis and lactation. (luetteke1999targetedinactivationof pages 1-2, luetteke1999targetedinactivationof pages 6-7)
In vivo pharmacologic EGFR inhibition. EGFR inhibitors with clinical use (e.g., gefitinib) are applied in mouse models to modulate EGFR-dependent tissue remodeling (e.g., the hippocampal neurogenic niche after seizures). (pastoralonso2024hbegfactivatesegfr pages 1-2)
Live biosensor imaging of ERK dynamics. ERK-biosensor mice enable quantitative measurement of EGFR-ligand-dependent ERK waves during physiological processes such as epidermal wound repair, supporting systems-level modeling of ligand diffusion/activation. (deguchi2024lowaffinityligandsof pages 1-4)
Ligand redundancy is a core principle. Multiple authoritative reviews and mouse genetics papers converge on the conclusion that 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. (luetteke1999targetedinactivationof pages 1-2, sibilia2007theepidermalgrowth pages 2-4)
Tissue-specific processing is central to Egf biology. The classical mouse precursor studies and later review emphasize that distinct tissues (submaxillary gland vs kidney) handle the same precursor very differently—salivary gland efficiently produces mature EGF for secretion, whereas kidney exhibits membrane-associated proEGF and urinary high-MW forms, implying regulated or incomplete maturation/shedding. This has major implications for annotating Egf’s “site of action”: in many tissues it may function as a membrane-anchored ligand reservoir rather than a source of abundant soluble 6 kDa EGF. (scott1985thestructureand pages 4-7, lakshmanan1990identificationofproepidermal pages 1-3, zeng2014epidermalgrowthfactor pages 2-4)
Recency gap for Egf-specific primary work. The most definitive mechanistic and localization evidence for mouse Egf/proEGF in the retrieved texts is classic (1985–1990) with a consolidating review (2014). Recent (2023–2024) work retrieved here is largely EGFR-ligand-field focused or emphasizes other ligands (e.g., HB-EGF, EREG), and therefore should be used to contextualize Egf rather than replace Egf-specific evidence. (scott1985thestructureand pages 4-7, zeng2014epidermalgrowthfactor pages 2-4, deguchi2024lowaffinityligandsof pages 1-4, pastoralonso2024hbegfactivatesegfr pages 1-2)
Sheddase specificity is context-dependent. A 2024 preprint summarizes probe-based evidence that ADAM17 sheds many EGFR ligands but not EGF in that experimental setup; this does not exclude other proteases or contexts for proEGF processing (as illustrated by platelet ADAMDEC1-mediated cleavage in a different system). (deguchi2024lowaffinityligandsof pages 1-4, chen2017thesolubleprotease pages 1-2)
References
(scott1985thestructureand pages 1-4): J. Scott, S. Patterson, L. Rall, G. I. Bell, R. Crawford, J. Penschow, H. Niall, and J. Coghlan. The structure and biosynthesis of epidermal growth factor precursor. Journal of Cell Science, 1985:19-28, Feb 1985. URL: https://doi.org/10.1242/jcs.1985.supplement_3.3, doi:10.1242/jcs.1985.supplement_3.3. This article has 64 citations and is from a domain leading peer-reviewed journal.
(zeng2014epidermalgrowthfactor pages 2-4): Fenghua Zeng and Raymond C. Harris. Epidermal growth factor, from gene organization to bedside. Seminars in cell & developmental biology, 28:2-11, Apr 2014. URL: https://doi.org/10.1016/j.semcdb.2014.01.011, doi:10.1016/j.semcdb.2014.01.011. This article has 311 citations and is from a peer-reviewed journal.
(zeng2014epidermalgrowthfactor pages 2-2): Fenghua Zeng and Raymond C. Harris. Epidermal growth factor, from gene organization to bedside. Seminars in cell & developmental biology, 28:2-11, Apr 2014. URL: https://doi.org/10.1016/j.semcdb.2014.01.011, doi:10.1016/j.semcdb.2014.01.011. This article has 311 citations and is from a peer-reviewed journal.
(scott1985thestructureand pages 4-7): J. Scott, S. Patterson, L. Rall, G. I. Bell, R. Crawford, J. Penschow, H. Niall, and J. Coghlan. The structure and biosynthesis of epidermal growth factor precursor. Journal of Cell Science, 1985:19-28, Feb 1985. URL: https://doi.org/10.1242/jcs.1985.supplement_3.3, doi:10.1242/jcs.1985.supplement_3.3. This article has 64 citations and is from a domain leading peer-reviewed journal.
(scott1985thestructureand media d2d35de8): J. Scott, S. Patterson, L. Rall, G. I. Bell, R. Crawford, J. Penschow, H. Niall, and J. Coghlan. The structure and biosynthesis of epidermal growth factor precursor. Journal of Cell Science, 1985:19-28, Feb 1985. URL: https://doi.org/10.1242/jcs.1985.supplement_3.3, doi:10.1242/jcs.1985.supplement_3.3. This article has 64 citations and is from a domain leading peer-reviewed journal.
(chen2017thesolubleprotease pages 1-2): Rui Chen, Ge Jin, and Thomas M. McIntyre. The soluble protease adamdec1 released from activated platelets hydrolyzes platelet membrane pro-epidermal growth factor (egf) to active high-molecular-weight egf. Journal of Biological Chemistry, 292:10112-10122, Jun 2017. URL: https://doi.org/10.1074/jbc.m116.771642, doi:10.1074/jbc.m116.771642. This article has 40 citations and is from a domain leading peer-reviewed journal.
(lakshmanan1990identificationofproepidermal pages 1-3): J. Lakshmanan, E.C. Salido, R. Lam, L. Barajas, and D.A. Fisher. Identification of pro-epidermal growth factor and high molecular weight epidermal growth factors in adult mouse urine. Biochemical and biophysical research communications, 173 3:902-11, Dec 1990. URL: https://doi.org/10.1016/s0006-291x(05)80871-x, doi:10.1016/s0006-291x(05)80871-x. This article has 20 citations and is from a peer-reviewed journal.
(fisher1990metabolismandeffects pages 2-3): DELBERT A. FISHER and JAYARAMAN LAKSHMANAN. Metabolism and effects of epidermal growth factor and related growth factors in mammals. Endocrine reviews, 11 3:418-42, Aug 1990. URL: https://doi.org/10.1210/edrv-11-3-418, doi:10.1210/edrv-11-3-418. This article has 510 citations and is from a domain leading peer-reviewed journal.
(luetteke1999targetedinactivationof pages 1-2): Noreen C. Luetteke, Ting Hu Qiu, Suzanne E. Fssssenton, Kelly L. Troyer, Richard F. Riedel, Aileen Chang, and David C. Lee. Targeted inactivation of the egf and amphiregulin genes reveals distinct roles for egf receptor ligands in mouse mammary gland development. Development, 126:2739-2750, Jun 1999. URL: https://doi.org/10.1242/dev.126.12.2739, doi:10.1242/dev.126.12.2739. This article has 698 citations and is from a domain leading peer-reviewed journal.
(sibilia2007theepidermalgrowth pages 2-4): Maria Sibilia, Renate Kroismayr, Beate M. Lichtenberger, Anuradha Natarajan, Manfred Hecking, and Martin Holcmann. The epidermal growth factor receptor: from development to tumorigenesis. Differentiation; research in biological diversity, 75 9:770-87, Nov 2007. URL: https://doi.org/10.1111/j.1432-0436.2007.00238.x, doi:10.1111/j.1432-0436.2007.00238.x. This article has 468 citations.
(luetteke1999targetedinactivationof pages 2-3): Noreen C. Luetteke, Ting Hu Qiu, Suzanne E. Fssssenton, Kelly L. Troyer, Richard F. Riedel, Aileen Chang, and David C. Lee. Targeted inactivation of the egf and amphiregulin genes reveals distinct roles for egf receptor ligands in mouse mammary gland development. Development, 126:2739-2750, Jun 1999. URL: https://doi.org/10.1242/dev.126.12.2739, doi:10.1242/dev.126.12.2739. This article has 698 citations and is from a domain leading peer-reviewed journal.
(luetteke1999targetedinactivationof pages 6-7): Noreen C. Luetteke, Ting Hu Qiu, Suzanne E. Fssssenton, Kelly L. Troyer, Richard F. Riedel, Aileen Chang, and David C. Lee. Targeted inactivation of the egf and amphiregulin genes reveals distinct roles for egf receptor ligands in mouse mammary gland development. Development, 126:2739-2750, Jun 1999. URL: https://doi.org/10.1242/dev.126.12.2739, doi:10.1242/dev.126.12.2739. This article has 698 citations and is from a domain leading peer-reviewed journal.
(chan2000expressionofepidermal pages 1-2): Siu-Yuen Chan and Richard Wing-Chuen Wong. Expression of epidermal growth factor in transgenic mice causes growth retardation*. The Journal of Biological Chemistry, 275:38693-38698, Dec 2000. URL: https://doi.org/10.1074/jbc.m004189200, doi:10.1074/jbc.m004189200. This article has 108 citations.
(deguchi2024lowaffinityligandsof pages 1-4): Eriko Deguchi, Shuhao Lin, Daiki Hirayama, Kimiya Matsuda, Akira Tanave, Kenta Sumiyama, Shinya Tsukiji, Tetsuhisa Otani, Mikio Furuse, Alexander Sorkin, Michiyuki Matsuda, and Kenta Terai. Low-affinity ligands of the epidermal growth factor receptor are long-range signal transmitters during collective cell migration of epithelial cells. bioRxiv, Sep 2024. URL: https://doi.org/10.1101/2024.09.25.614853, doi:10.1101/2024.09.25.614853. This article has 1 citations.
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(li2024egfstat1maintainedecm1expression pages 1-5): Yujia Li, F. Link, Weiguo Fan, R. Feng, W. Piorońska, Z. Nwosu, K. Gould, C. Meyer, Seddik Hammad, H. Weng, Matthias P. Ebert, Steven Dooley, and Sai Wang. Egf/stat1-maintained ecm1 expression in hepatic homeostasis is disrupted by ifnγ/nrf2 in chronic liver diseases. 40. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, Jan 2024. URL: https://doi.org/10.1055/s-0043-1777485, doi:10.1055/s-0043-1777485. This article has 0 citations.
id: P01132
gene_symbol: Egf
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:10090
label: Mus musculus
description: 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.
existing_annotations:
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0043410
label: positive regulation of MAPK cascade
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation.
action: KEEP_AS_NON_CORE
reason: Receptor-mediated MAPK activation, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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.
action: ACCEPT
reason: Precursor is a type I plasma-membrane protein.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008083
label: growth factor activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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.
action: ACCEPT
reason: 'Core ligand MF: EGF is the prototypical growth factor.'
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005154
label: epidermal growth factor receptor binding
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
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.
action: ACCEPT
reason: Core, specific receptor-binding MF for the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: classifying EGF among high-affinity ligands (apparent **Kd 0.1–1 nM**)
- term:
id: GO:0005509
label: calcium ion binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
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.
action: KEEP_AS_NON_CORE
reason: Structural Ca-binding of precursor EGF-Ca domains.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: EGF-like_Ca-bd_dom. (IPR001881)
- term:
id: GO:0008083
label: growth factor activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
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.
action: ACCEPT
reason: 'Core ligand MF: EGF is the prototypical growth factor.'
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0010604
label: positive regulation of macromolecule metabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: Generic high-level metabolic-regulation term covered by more specific transcription/biosynthesis annotations; uninformative as standalone.
action: MARK_AS_OVER_ANNOTATED
reason: Over-broad metabolic-regulation parent.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport.
- term:
id: GO:0016020
label: membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: Bare 'membrane' under-specifies; pro-EGF is a type I plasma-membrane protein, so plasma membrane is the correct specific cellular component.
action: MODIFY
reason: Generic CC; precursor is plasma-membrane anchored.
proposed_replacement_terms:
- id: GO:0005886
label: plasma membrane
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048513
label: animal organ development
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: Over-broad parent developmental term.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048731
label: system development
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: Very high-level developmental term with little specificity for a single redundant EGFR ligand; over-annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Over-broad developmental grouping term.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0051049
label: regulation of transport
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: Generic high-level transport-regulation term; specific trafficking/ion annotations already capture the meaningful biology, so this parent is over-annotated.
action: MARK_AS_OVER_ANNOTATED
reason: Over-broad transport-regulation parent.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis.
- term:
id: GO:0071944
label: cell periphery
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
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.
action: MODIFY
reason: Too generic; specific plasma membrane known.
proposed_replacement_terms:
- id: GO:0005886
label: plasma membrane
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0080090
label: regulation of primary metabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: Very broad metabolic-regulation grouping term added electronically; provides no specific functional insight for EGF.
action: MARK_AS_OVER_ANNOTATED
reason: Over-broad metabolic-regulation parent.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport.
- term:
id: GO:0001525
label: angiogenesis
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: KEEP_AS_NON_CORE
reason: Developmental angiogenesis, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0001938
label: positive regulation of endothelial cell proliferation
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF/EGFR signaling can promote endothelial proliferation in angiogenic contexts; a downstream tissue-specific output, non-core.
action: KEEP_AS_NON_CORE
reason: Endothelial proliferation, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0002092
label: positive regulation of receptor internalization
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF binding triggers EGFR endocytosis/internalization for signal attenuation; a downstream trafficking consequence of ligand engagement, non-core MF.
action: KEEP_AS_NON_CORE
reason: Ligand-induced receptor endocytosis, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis.
- term:
id: GO:0005085
label: guanyl-nucleotide exchange factor activity
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: REMOVE
reason: Ligand is not a GEF; contradicted by biology.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008083
label: growth factor activity
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: ACCEPT
reason: 'Core ligand MF: EGF is the prototypical growth factor.'
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0010595
label: positive regulation of endothelial cell migration
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF/EGFR signaling can promote endothelial migration in angiogenic/wound contexts; tissue-specific downstream effect, non-core.
action: KEEP_AS_NON_CORE
reason: Endothelial migration, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF stimulation alters expression of many genes via EGFR-driven cascades; a generic downstream output retained as non-core.
action: KEEP_AS_NON_CORE
reason: Generic downstream gene-expression change.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport.
- term:
id: GO:0010800
label: positive regulation of peptidyl-threonine phosphorylation
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF-driven kinase cascades (e.g., MAPK) increase threonine phosphorylation of substrates; a downstream signaling consequence, non-core for the ligand.
action: KEEP_AS_NON_CORE
reason: Downstream Thr-phospho via cascade, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0030335
label: positive regulation of cell migration
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF promotes cell motility/migration via EGFR (e.g., epithelial wound repair); a pleiotropic downstream output rather than core ligand MF.
action: KEEP_AS_NON_CORE
reason: Pro-migratory output, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: in vivo, EREG-deficient ERK-biosensor mice show impaired ERK wave propagation and cell migration during skin wound repair.
- term:
id: GO:0042327
label: positive regulation of phosphorylation
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF broadly increases protein phosphorylation through EGFR-initiated cascades; a generic downstream regulatory effect, retained as non-core.
action: KEEP_AS_NON_CORE
reason: Generic downstream phosphorylation increase.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0043410
label: positive regulation of MAPK cascade
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation.
action: KEEP_AS_NON_CORE
reason: Receptor-mediated MAPK activation, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0045840
label: positive regulation of mitotic nuclear division
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: As a mitogen, EGF promotes cell-cycle progression and mitosis downstream of EGFR; a pleiotropic consequence of receptor activation, non-core.
action: KEEP_AS_NON_CORE
reason: Mitogenic output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0045893
label: positive regulation of DNA-templated transcription
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF-induced signaling activates transcription factors and gene programs downstream of EGFR; a far-downstream nuclear consequence, non-core for the secreted ligand.
action: KEEP_AS_NON_CORE
reason: Downstream transcriptional activation, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport.
- term:
id: GO:0051048
label: negative regulation of secretion
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF can modulate secretory processes downstream of receptor signaling; a pleiotropic physiological effect, non-core.
action: KEEP_AS_NON_CORE
reason: Secretion modulation, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0051897
label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: PI3K/AKT activation is a canonical EGFR-downstream branch stimulated by EGF; downstream regulatory effect rather than core ligand activity.
action: KEEP_AS_NON_CORE
reason: PI3K/AKT branch downstream of EGFR.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: KEEP_AS_NON_CORE
reason: Secondary secretory compartment, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: membrane-anchored ligand reservoir
- term:
id: GO:0070371
label: ERK1 and ERK2 cascade
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: KEEP_AS_NON_CORE
reason: Downstream MAPK cascade, receptor-driven.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0090263
label: positive regulation of canonical Wnt signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: KEEP_AS_NON_CORE
reason: Cross-talk effect on Wnt, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0090279
label: regulation of calcium ion import
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: KEEP_AS_NON_CORE
reason: Renal/cellular Ca ion-handling, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:1900127
label: positive regulation of hyaluronan biosynthetic process
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF/EGFR signaling can upregulate hyaluronan synthesis; a specific downstream metabolic output, non-core for the ligand.
action: KEEP_AS_NON_CORE
reason: Hyaluronan synthesis upregulation, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:1902966
label: positive regulation of protein localization to early endosome
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Following EGF binding, internalized EGFR traffics to early endosomes; a downstream trafficking event consequent to receptor activation, non-core.
action: KEEP_AS_NON_CORE
reason: Endosomal receptor trafficking, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis.
- term:
id: GO:1905278
label: positive regulation of epithelial tube formation
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGFR-ligand signaling supports epithelial tubulogenesis/branching; a developmental morphogenetic output downstream of the receptor, non-core.
action: KEEP_AS_NON_CORE
reason: Epithelial tubulogenesis, developmental output.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:2000008
label: regulation of protein localization to cell surface
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: EGF signaling modulates cell-surface protein localization (e.g., receptor/transporter trafficking); a downstream regulatory effect, non-core.
action: KEEP_AS_NON_CORE
reason: Surface-localization regulation, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis.
- term:
id: GO:0001525
label: angiogenesis
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
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.
action: KEEP_AS_NON_CORE
reason: Developmental angiogenesis, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0001938
label: positive regulation of endothelial cell proliferation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF/EGFR signaling can promote endothelial proliferation in angiogenic contexts; a downstream tissue-specific output, non-core.
action: KEEP_AS_NON_CORE
reason: Endothelial proliferation, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0002092
label: positive regulation of receptor internalization
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF binding triggers EGFR endocytosis/internalization for signal attenuation; a downstream trafficking consequence of ligand engagement, non-core MF.
action: KEEP_AS_NON_CORE
reason: Ligand-induced receptor endocytosis, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis.
- term:
id: GO:0005085
label: guanyl-nucleotide exchange factor activity
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
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.
action: REMOVE
reason: Ligand is not a GEF; contradicted by biology.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**
- term:
id: GO:0005615
label: extracellular space
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0010595
label: positive regulation of endothelial cell migration
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF/EGFR signaling can promote endothelial migration in angiogenic/wound contexts; tissue-specific downstream effect, non-core.
action: KEEP_AS_NON_CORE
reason: Endothelial migration, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF stimulation alters expression of many genes via EGFR-driven cascades; a generic downstream output retained as non-core.
action: KEEP_AS_NON_CORE
reason: Generic downstream gene-expression change.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport.
- term:
id: GO:0030297
label: transmembrane receptor protein tyrosine kinase activator activity
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
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.
action: ACCEPT
reason: 'Core: ligand activates the RTK EGFR.'
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0030335
label: positive regulation of cell migration
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF promotes cell motility/migration via EGFR (e.g., epithelial wound repair); a pleiotropic downstream output rather than core ligand MF.
action: KEEP_AS_NON_CORE
reason: Pro-migratory output, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: in vivo, EREG-deficient ERK-biosensor mice show impaired ERK wave propagation and cell migration during skin wound repair.
- term:
id: GO:0038134
label: ERBB2-EGFR signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
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.
action: KEEP_AS_NON_CORE
reason: Receptor heterodimer signaling, downstream of ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0042327
label: positive regulation of phosphorylation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF broadly increases protein phosphorylation through EGFR-initiated cascades; a generic downstream regulatory effect, retained as non-core.
action: KEEP_AS_NON_CORE
reason: Generic downstream phosphorylation increase.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0043410
label: positive regulation of MAPK cascade
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation.
action: KEEP_AS_NON_CORE
reason: Receptor-mediated MAPK activation, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0045840
label: positive regulation of mitotic nuclear division
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: As a mitogen, EGF promotes cell-cycle progression and mitosis downstream of EGFR; a pleiotropic consequence of receptor activation, non-core.
action: KEEP_AS_NON_CORE
reason: Mitogenic output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0045893
label: positive regulation of DNA-templated transcription
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF-induced signaling activates transcription factors and gene programs downstream of EGFR; a far-downstream nuclear consequence, non-core for the secreted ligand.
action: KEEP_AS_NON_CORE
reason: Downstream transcriptional activation, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport.
- term:
id: GO:0048018
label: receptor ligand activity
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
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.
action: ACCEPT
reason: Core agonist ligand MF.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0051048
label: negative regulation of secretion
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF can modulate secretory processes downstream of receptor signaling; a pleiotropic physiological effect, non-core.
action: KEEP_AS_NON_CORE
reason: Secretion modulation, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0051897
label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: PI3K/AKT activation is a canonical EGFR-downstream branch stimulated by EGF; downstream regulatory effect rather than core ligand activity.
action: KEEP_AS_NON_CORE
reason: PI3K/AKT branch downstream of EGFR.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
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.
action: KEEP_AS_NON_CORE
reason: Secondary secretory compartment, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: membrane-anchored ligand reservoir
- term:
id: GO:0070371
label: ERK1 and ERK2 cascade
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
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.
action: KEEP_AS_NON_CORE
reason: Downstream MAPK cascade, receptor-driven.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0090263
label: positive regulation of canonical Wnt signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
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.
action: KEEP_AS_NON_CORE
reason: Cross-talk effect on Wnt, pleiotropic.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0090279
label: regulation of calcium ion import
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
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.
action: KEEP_AS_NON_CORE
reason: Renal/cellular Ca ion-handling, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:1900127
label: positive regulation of hyaluronan biosynthetic process
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF/EGFR signaling can upregulate hyaluronan synthesis; a specific downstream metabolic output, non-core for the ligand.
action: KEEP_AS_NON_CORE
reason: Hyaluronan synthesis upregulation, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:1902966
label: positive regulation of protein localization to early endosome
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: Following EGF binding, internalized EGFR traffics to early endosomes; a downstream trafficking event consequent to receptor activation, non-core.
action: KEEP_AS_NON_CORE
reason: Endosomal receptor trafficking, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis.
- term:
id: GO:1905278
label: positive regulation of epithelial tube formation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGFR-ligand signaling supports epithelial tubulogenesis/branching; a developmental morphogenetic output downstream of the receptor, non-core.
action: KEEP_AS_NON_CORE
reason: Epithelial tubulogenesis, developmental output.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:2000008
label: regulation of protein localization to cell surface
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: EGF signaling modulates cell-surface protein localization (e.g., receptor/transporter trafficking); a downstream regulatory effect, non-core.
action: KEEP_AS_NON_CORE
reason: Surface-localization regulation, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis.
- term:
id: GO:0005615
label: extracellular space
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005154
label: epidermal growth factor receptor binding
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
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.
action: ACCEPT
reason: Core, specific receptor-binding MF for the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: classifying EGF among high-affinity ligands (apparent **Kd 0.1–1 nM**)
- term:
id: GO:0005615
label: extracellular space
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048146
label: positive regulation of fibroblast proliferation
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: EGF stimulates proliferation of some fibroblasts in culture; a tissue-specific downstream proliferative effect, non-core.
action: KEEP_AS_NON_CORE
reason: Fibroblast proliferation, tissue-specific output.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0070374
label: positive regulation of ERK1 and ERK2 cascade
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
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.
action: KEEP_AS_NON_CORE
reason: Positive ERK regulation via receptor, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:2000573
label: positive regulation of DNA biosynthetic process
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: As a mitogen, EGF promotes DNA replication during cell-cycle entry; a downstream proliferative consequence, non-core.
action: KEEP_AS_NON_CORE
reason: DNA synthesis as mitogenic readout.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0030297
label: transmembrane receptor protein tyrosine kinase activator activity
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
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.
action: ACCEPT
reason: 'Core: ligand activates the RTK EGFR.'
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0043410
label: positive regulation of MAPK cascade
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation.
action: KEEP_AS_NON_CORE
reason: Receptor-mediated MAPK activation, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048018
label: receptor ligand activity
evidence_type: IDA
original_reference_id: PMID:11823423
review:
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.
action: ACCEPT
reason: Core agonist ligand MF.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048018
label: receptor ligand activity
evidence_type: IDA
original_reference_id: PMID:14627991
review:
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.
action: ACCEPT
reason: Core agonist ligand MF.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005615
label: extracellular space
evidence_type: IDA
original_reference_id: PMID:12761849
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:12761849
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:9529375
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048018
label: receptor ligand activity
evidence_type: IDA
original_reference_id: PMID:12761849
review:
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.
action: ACCEPT
reason: Core agonist ligand MF.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048018
label: receptor ligand activity
evidence_type: IDA
original_reference_id: PMID:9529375
review:
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.
action: ACCEPT
reason: Core agonist ligand MF.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005615
label: extracellular space
evidence_type: ISO
original_reference_id: PMID:11336639
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005615
label: extracellular space
evidence_type: IDA
original_reference_id: PMID:22822073
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005615
label: extracellular space
evidence_type: IDA
original_reference_id: PMID:6248866
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005615
label: extracellular space
evidence_type: IDA
original_reference_id: PMID:7752576
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0038134
label: ERBB2-EGFR signaling pathway
evidence_type: ISO
original_reference_id: PMID:11336639
review:
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.
action: KEEP_AS_NON_CORE
reason: Receptor heterodimer signaling, downstream of ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0038134
label: ERBB2-EGFR signaling pathway
evidence_type: IDA
original_reference_id: PMID:22822073
review:
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.
action: KEEP_AS_NON_CORE
reason: Receptor heterodimer signaling, downstream of ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048018
label: receptor ligand activity
evidence_type: ISO
original_reference_id: PMID:11336639
review:
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.
action: ACCEPT
reason: Core agonist ligand MF.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048018
label: receptor ligand activity
evidence_type: IDA
original_reference_id: PMID:22822073
review:
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.
action: ACCEPT
reason: Core agonist ligand MF.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:6248866
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:7752576
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048018
label: receptor ligand activity
evidence_type: IDA
original_reference_id: PMID:6248866
review:
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.
action: ACCEPT
reason: Core agonist ligand MF.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048018
label: receptor ligand activity
evidence_type: IDA
original_reference_id: PMID:7752576
review:
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.
action: ACCEPT
reason: Core agonist ligand MF.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0043410
label: positive regulation of MAPK cascade
evidence_type: IDA
original_reference_id: PMID:16339969
review:
summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation.
action: KEEP_AS_NON_CORE
reason: Receptor-mediated MAPK activation, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0043410
label: positive regulation of MAPK cascade
evidence_type: IDA
original_reference_id: PMID:9030684
review:
summary: EGF promotes MAPK signaling through EGFR engagement; a well-supported but downstream/regulatory role secondary to receptor activation.
action: KEEP_AS_NON_CORE
reason: Receptor-mediated MAPK activation, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IDA
original_reference_id: PMID:8702723
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005154
label: epidermal growth factor receptor binding
evidence_type: IDA
original_reference_id: PMID:7678348
review:
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.
action: ACCEPT
reason: Core, specific receptor-binding MF for the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: classifying EGF among high-affinity ligands (apparent **Kd 0.1–1 nM**)
- term:
id: GO:0061098
label: positive regulation of protein tyrosine kinase activity
evidence_type: IDA
original_reference_id: PMID:7678348
review:
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.
action: KEEP_AS_NON_CORE
reason: Activates kinases downstream; non-core BP.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0050731
label: positive regulation of peptidyl-tyrosine phosphorylation
evidence_type: IDA
original_reference_id: PMID:21186272
review:
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.
action: KEEP_AS_NON_CORE
reason: Regulatory (not catalytic) tyrosine-phospho effect.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0043388
label: positive regulation of DNA binding
evidence_type: IDA
original_reference_id: PMID:15156153
review:
summary: EGF signaling increases DNA-binding activity of downstream transcription factors; a distal nuclear regulatory consequence of receptor activation, non-core.
action: KEEP_AS_NON_CORE
reason: Downstream TF DNA-binding effect.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: shaping cell proliferation, differentiation and apoptosis and broader physiology such as organ development, regeneration and ion transport.
- term:
id: GO:0046425
label: regulation of receptor signaling pathway via JAK-STAT
evidence_type: IDA
original_reference_id: PMID:15156153
review:
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.
action: KEEP_AS_NON_CORE
reason: JAK-STAT cross-talk downstream of EGFR.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: Stat5a phosphorylation was conspicuously decreased in AR-deficient contexts (especially double/triple nulls), linking EGFR-ligand signaling to lactation-associated STAT activation.
- term:
id: GO:0090370
label: negative regulation of cholesterol efflux
evidence_type: IDA
original_reference_id: PMID:20037141
review:
summary: An IDA-supported specific metabolic effect of EGF signaling on cholesterol efflux; a narrow downstream physiological output, non-core for the ligand.
action: KEEP_AS_NON_CORE
reason: Specific cholesterol-efflux effect, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:2000060
label: positive regulation of ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:20208556
review:
summary: EGF binding leads to ubiquitination and lysosomal/proteasomal degradation of activated EGFR; an IDA-supported downstream catabolic consequence, non-core.
action: KEEP_AS_NON_CORE
reason: Ligand-triggered receptor degradation, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis.
- term:
id: GO:0051223
label: regulation of protein transport
evidence_type: ISO
original_reference_id: PMID:19723622
review:
summary: EGF-initiated signaling regulates intracellular protein transport/trafficking; a pleiotropic downstream effect, non-core for the ligand.
action: KEEP_AS_NON_CORE
reason: Protein-transport regulation, downstream.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: receptor complexes are internalized and degraded in lysosomes, and prolonged receptor occupancy can be required for mitogenesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17626015
review:
summary: Bare 'protein binding' is uninformative; the specific and curated 'epidermal growth factor receptor binding' captures the meaningful interaction. Always over-annotated.
action: MARK_AS_OVER_ANNOTATED
reason: Generic MF superseded by EGFR-binding term.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: The primary molecular function of EGF (and in some contexts proEGF) is **binding to EGFR (ErbB1/HER1)**
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:17626015
review:
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.
action: ACCEPT
reason: Precursor is a type I plasma-membrane protein.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008083
label: growth factor activity
evidence_type: ISO
original_reference_id: GO_REF:0000008
review:
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.
action: ACCEPT
reason: 'Core ligand MF: EGF is the prototypical growth factor.'
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: ISO
original_reference_id: GO_REF:0000008
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005154
label: epidermal growth factor receptor binding
evidence_type: IDA
original_reference_id: PMID:6315706
review:
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.
action: ACCEPT
reason: Core, specific receptor-binding MF for the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: classifying EGF among high-affinity ligands (apparent **Kd 0.1–1 nM**)
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:6315706
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0060749
label: mammary gland alveolus development
evidence_type: IGI
original_reference_id: PMID:10331984
review:
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.
action: KEEP_AS_NON_CORE
reason: Mammary alveolar development, genetic support.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: In the Egf/Areg/Tgfa combinatorial knockout framework, amphiregulin is essential for pubertal ductal outgrowth, while EGF and TGFα support lactogenesis.
- term:
id: GO:0005576
label: extracellular region
evidence_type: TAS
original_reference_id: Reactome:R-MMU-179883
review:
summary: The processed mature EGF peptide is released and acts in the extracellular region; secreted localization is core to a diffusible growth-factor ligand.
action: ACCEPT
reason: 'Core: secreted ligand acts extracellularly.'
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-MMU-179883
review:
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.
action: ACCEPT
reason: Precursor is a type I plasma-membrane protein.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005615
label: extracellular space
evidence_type: IDA
original_reference_id: PMID:7641815
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: IGI
original_reference_id: PMID:7641815
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IGI
original_reference_id: PMID:7641815
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0021940
label: positive regulation of cerebellar granule cell precursor proliferation
evidence_type: IDA
original_reference_id: PMID:10027293
review:
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.
action: KEEP_AS_NON_CORE
reason: Narrow neural proliferative output, non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IGI
original_reference_id: PMID:15051883
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0048754
label: branching morphogenesis of an epithelial tube
evidence_type: IDA
original_reference_id: PMID:15831470
review:
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.
action: KEEP_AS_NON_CORE
reason: Branching morphogenesis, developmental; keep non-core.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: In the Egf/Areg/Tgfa combinatorial knockout framework, amphiregulin is essential for pubertal ductal outgrowth, while EGF and TGFα support lactogenesis.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:15695332
review:
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.
action: ACCEPT
reason: Core pathway initiated by the ligand.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IDA
original_reference_id: PMID:15695332
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IDA
original_reference_id: PMID:14712229
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IGI
original_reference_id: PMID:15509736
review:
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.
action: KEEP_AS_NON_CORE
reason: Proliferative output downstream of receptor.
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005615
label: extracellular space
evidence_type: IDA
original_reference_id: PMID:8240367
review:
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.
action: ACCEPT
reason: Core secreted localization (IDA-supported).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0018108
label: peptidyl-tyrosine phosphorylation
evidence_type: IDA
original_reference_id: PMID:14561752
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: Catalytic process belongs to the receptor; over-annotation of the ligand (downgraded from REMOVE as it carries IDA evidence).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- term:
id: GO:0050730
label: regulation of peptidyl-tyrosine phosphorylation
evidence_type: IDA
original_reference_id: PMID:11940581
review:
summary: By binding and activating EGFR, EGF positively regulates downstream peptidyl-tyrosine phosphorylation; a real regulatory effect of the ligand.
action: KEEP_AS_NON_CORE
reason: Downstream regulatory effect of ligand-receptor engagement; non-core (experimental IDA retained).
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings: []
- id: GO_REF:0000008
title: Gene Ontology annotation by the MGI curatorial staff, curated orthology
findings: []
- id: GO_REF:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000096
title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000119
title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:10027293
title: Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog.
findings: []
- id: PMID:10331984
title: Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development.
findings: []
- id: PMID:11336639
title: Heterodimerization of the epidermal-growth-factor (EGF) receptor and ErbB2 and the affinity of EGF binding are regulated by different mechanisms.
findings: []
- id: PMID:11823423
title: A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.
findings: []
- id: PMID:11940581
title: Protein kinase C-alpha and protein kinase C-epsilon are required for Grb2-associated binder-1 tyrosine phosphorylation in response to platelet-derived growth factor.
findings: []
- id: PMID:12761849
title: EGF-stimulated signaling by means of PI3K, PLCgamma1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular gland.
findings: []
- id: PMID:14561752
title: N-acetylglucosaminyltransferase V expression levels regulate cadherin-associated homotypic cell-cell adhesion and intracellular signaling pathways.
findings: []
- id: PMID:14627991
title: Serine mutations that abrogate ligand-induced ubiquitination and internalization of the EGF receptor do not affect c-Cbl association with the receptor.
findings: []
- id: PMID:14712229
title: 'G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway.'
findings: []
- id: PMID:15051883
title: Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor.
findings: []
- id: PMID:15156153
title: Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling.
findings: []
- id: PMID:15509736
title: Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in telencephalic progenitors.
findings: []
- id: PMID:15695332
title: Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling.
findings: []
- id: PMID:15831470
title: Integrin-linked kinase mediates bone morphogenetic protein 7-dependent renal epithelial cell morphogenesis.
findings: []
- id: PMID:16339969
title: Efficient suppression of FGF-2-induced ERK activation by the cooperative interaction among mammalian Sprouty isoforms.
findings: []
- id: PMID:17626015
title: SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15.
findings: []
- id: PMID:19723622
title: 'Activator of G protein signaling 8 (AGS8) is required for hypoxia-induced apoptosis of cardiomyocytes: role of G betagamma and connexin 43 (CX43).'
findings: []
- id: PMID:20037141
title: Inhibition of ERK1/2 and activation of liver X receptor synergistically induce macrophage ABCA1 expression and cholesterol efflux.
findings: []
- id: PMID:20208556
title: Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7.
findings: []
- id: PMID:21186272
title: Activation of the neuregulin/ErbB system during physiological ventricular remodeling in pregnancy.
findings: []
- id: PMID:22822073
title: Quantitation of the effect of ErbB2 on epidermal growth factor receptor binding and dimerization.
findings: []
- id: PMID:6248866
title: Detection of epidermal growth factor-urogastrone and its receptor during fetal mouse development.
findings: []
- id: PMID:6315706
title: Epidermal growth factor-like transforming growth factor. II. Interaction with epidermal growth factor receptors in human placenta membranes and A431 cells.
findings: []
- id: PMID:7641815
title: Altering the expression of cell surface beta 1,4-galactosyltransferase modulates cell growth.
findings: []
- id: PMID:7678348
title: Expression of the epidermal growth factor receptor gene is regulated in mouse blastocysts during delayed implantation.
findings: []
- id: PMID:7752576
title: Tyrosine kinase activity of the EGF receptor in murine metanephric organ culture.
findings: []
- id: PMID:8240367
title: An inborn error in epidermal growth factor prohormone metabolism in a mouse model of autosomal recessive polycystic kidney disease.
findings: []
- id: PMID:8702723
title: The epidermal growth factor receptor couples transforming growth factor-alpha, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4.
findings: []
- id: PMID:9030684
title: Mutation in Sos1 dominantly enhances a weak allele of the EGFR, demonstrating a requirement for Sos1 in EGFR signaling and development.
findings: []
- id: PMID:9529375
title: Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse embryonic fibroblasts.
findings: []
- id: Reactome:R-MMU-179883
title: Mouse pro-EGF is cleaved by ADAM sheddases
findings: []
- id: UniProt:P01132
title: UniProt record for Egf (P01132)
findings: []
- id: file:mouse/Egf/Egf-deep-research-falcon.md
title: Deep research report on Egf (falcon)
findings: []
core_functions:
- molecular_function:
id: GO:0048018
label: receptor ligand activity
description: Processed EGF binds and activates EGFR-family receptors, promoting receptor dimerization and tyrosine kinase signaling.
locations:
- id: GO:0005576
label: extracellular region
- id: GO:0005886
label: plasma membrane
directly_involved_in:
- id: GO:0007173
label: epidermal growth factor receptor signaling pathway
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
- molecular_function:
id: GO:0005154
label: epidermal growth factor receptor binding
description: EGF directly engages EGFR to trigger receptor activation and downstream signal transduction.
locations:
- id: GO:0005576
label: extracellular region
directly_involved_in:
- id: GO:0007173
label: epidermal growth factor receptor signaling pathway
supported_by:
- reference_id: UniProt:P01132
supporting_text: '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.'
- reference_id: file:mouse/Egf/Egf-deep-research-falcon.md
supporting_text: 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.
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []