Existing Annotations Review

Core Functions

Processed EGF binds and activates EGFR-family receptors, promoting receptor dimerization and tyrosine kinase signaling.

Molecular Function:

receptor ligand activity

Directly Involved In:

epidermal growth factor receptor signaling pathway

Cellular Locations:

extracellular space 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
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.

EGF directly engages EGFR to trigger receptor activation and downstream signal transduction.

Molecular Function:

epidermal growth factor receptor binding

Directly Involved In:

epidermal growth factor receptor signaling pathway

Cellular Locations:

extracellular space

Supporting Evidence:

UniProt:P01132
FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro 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
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000008

Gene Ontology annotation by the MGI curatorial staff, curated orthology

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10027293

Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog.

PMID:10331984

Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development.

PMID:11336639

Heterodimerization of the epidermal-growth-factor (EGF) receptor and ErbB2 and the affinity of EGF binding are regulated by different mechanisms.

PMID:11823423

A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.

PMID:11940581

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.

PMID:12761849

EGF-stimulated signaling by means of PI3K, PLCgamma1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular gland.

PMID:14561752

N-acetylglucosaminyltransferase V expression levels regulate cadherin-associated homotypic cell-cell adhesion and intracellular signaling pathways.

PMID:14627991

Serine mutations that abrogate ligand-induced ubiquitination and internalization of the EGF receptor do not affect c-Cbl association with the receptor.

PMID:14712229

G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway.

PMID:15051883

Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor.

PMID:15156153

Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling.

PMID:15509736

Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in telencephalic progenitors.

PMID:15695332

Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling.

PMID:15831470

Integrin-linked kinase mediates bone morphogenetic protein 7-dependent renal epithelial cell morphogenesis.

PMID:16339969

Efficient suppression of FGF-2-induced ERK activation by the cooperative interaction among mammalian Sprouty isoforms.

PMID:17626015

SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15.

PMID:19723622

Activator of G protein signaling 8 (AGS8) is required for hypoxia-induced apoptosis of cardiomyocytes: role of G betagamma and connexin 43 (CX43).

PMID:20037141

Inhibition of ERK1/2 and activation of liver X receptor synergistically induce macrophage ABCA1 expression and cholesterol efflux.

PMID:20208556

Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7.

PMID:21186272

Activation of the neuregulin/ErbB system during physiological ventricular remodeling in pregnancy.

PMID:22822073

Quantitation of the effect of ErbB2 on epidermal growth factor receptor binding and dimerization.

PMID:6248866

Detection of epidermal growth factor-urogastrone and its receptor during fetal mouse development.

PMID:6315706

Epidermal growth factor-like transforming growth factor. II. Interaction with epidermal growth factor receptors in human placenta membranes and A431 cells.

PMID:7641815

Altering the expression of cell surface beta 1,4-galactosyltransferase modulates cell growth.

PMID:7678348

Expression of the epidermal growth factor receptor gene is regulated in mouse blastocysts during delayed implantation.

PMID:7752576

Tyrosine kinase activity of the EGF receptor in murine metanephric organ culture.

PMID:8240367

An inborn error in epidermal growth factor prohormone metabolism in a mouse model of autosomal recessive polycystic kidney disease.

PMID:8702723

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.

PMID:9030684

Mutation in Sos1 dominantly enhances a weak allele of the EGFR, demonstrating a requirement for Sos1 in EGFR signaling and development.

PMID:9529375

Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse embryonic fibroblasts.

Reactome:R-MMU-179883

Mouse pro-EGF is cleaved by ADAM sheddases

UniProt:P01132

UniProt record for Egf (P01132)

file:mouse/Egf/Egf-deep-research-falcon.md

Deep research report on Egf (falcon)

📚 Additional Documentation

Deep Research Falcon

(Egf-deep-research-falcon.md)

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gene_id: Egf
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RecName: Full=Epidermal growth factor; Flags: Precursor;'
gene_info: Name=Egf;
organism_full: Mus musculus (Mouse).
protein_family: Not specified in UniProt
protein_domains: 6-blade_b-propeller_TolB-like. (IPR011042); Cueball_EGF_LRP_Nidogen.
(IPR050778); EGF-like_Ca-bd_dom. (IPR001881); EGF-like_dom. (IPR000742); EGF-type_Asp/Asn_hydroxyl_site.
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P01132
Protein Description: RecName: Full=Pro-epidermal growth factor; Short=EGF; Contains: RecName: Full=Epidermal growth factor; Flags: Precursor;
Gene Information: Name=Egf;
Organism (full): Mus musculus (Mouse).
Protein Family: Not specified in UniProt
Key Domains: 6-blade_b-propeller_TolB-like. (IPR011042); Cueball_EGF_LRP_Nidogen. (IPR050778); EGF-like_Ca-bd_dom. (IPR001881); EGF-like_dom. (IPR000742); EGF-type_Asp/Asn_hydroxyl_site. (IPR000152)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Egf" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Egf' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene Egf (gene ID: Egf, UniProt: P01132) in mouse.

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.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P01132
Protein Description: RecName: Full=Pro-epidermal growth factor; Short=EGF; Contains: RecName: Full=Epidermal growth factor; Flags: Precursor;
Gene Information: Name=Egf;
Organism (full): Mus musculus (Mouse).
Protein Family: Not specified in UniProt
Key Domains: 6-blade_b-propeller_TolB-like. (IPR011042); Cueball_EGF_LRP_Nidogen. (IPR050778); EGF-like_Ca-bd_dom. (IPR001881); EGF-like_dom. (IPR000742); EGF-type_Asp/Asn_hydroxyl_site. (IPR000152)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Egf" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene Egf (gene ID: Egf, UniProt: P01132) in mouse.

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.

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.

Research report: Mouse Egf (UniProt P01132) — functional annotation of pro-epidermal growth factor (proEGF)

Scope and target verification

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.

1) Key concepts and definitions (current understanding)

1.1 What “Egf” encodes: a membrane-anchored ligand precursor

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)

1.2 “Processing/shedding” of EGFR ligands

“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)

1.3 Molecular function: EGFR ligand activity

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)

2) Protein architecture and subcellular localization

2.1 Architecture

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)

2.2 Localization: membrane association and tissue-specific compartments

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)

3) Expression patterns (where Egf is made)

3.1 Major sites of expression

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)

3.2 Sex dimorphism

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)

4) Biogenesis and processing: mature EGF vs high-molecular-weight forms

4.1 Salivary gland processing and regulated release

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)

4.2 Kidney: high mRNA but limited mature EGF, with urinary proEGF species

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)

4.3 Context-specific proteolysis: platelet proEGF cleavage as a mechanistic example

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)

5) Signaling pathways and biochemical roles

5.1 Canonical EGFR signaling pathways downstream of EGF

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)

5.2 Kidney functional interpretation: ion transport hypothesis

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)

6) In vivo genetics and phenotypes (mouse)

6.1 Egf loss-of-function is mild, indicating redundancy among EGFR ligands

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)

6.2 Combinatorial ligand loss unmasks roles in mammary gland differentiation and neonatal survival

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)

6.3 EGF overexpression is sufficient to cause growth defects

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)

7) Recent developments (prioritizing 2023–2024)

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.

7.1 2024: EGFR ligand affinity and long-range signaling in epithelia (wound repair context)

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)

7.2 2024: EGFR signaling in the adult hippocampal niche after seizures (ligand context: HB-EGF)

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)

7.3 2024: Proposed EGF/EGFR→STAT1 control of hepatocyte ECM1 (conference abstract)

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)

8) Current applications and real-world implementations

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)

9) Expert synthesis and interpretation (authoritative viewpoints)

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)

10) Key quantitative/statistical highlights (selected)

Precursor size: mouse prepro‑EGF 1217 aa; mature EGF 53 aa (~6–8 kDa). (zeng2014epidermalgrowthfactor pages 2-4, scott1985thestructureand pages 1-4)
Submaxillary gland EGF: adult male ~1000 ng/mg wet tissue vs female ~70 ng/mg (reviewed). (zeng2014epidermalgrowthfactor pages 2-2)
Plasma EGF: ~1 ng/mL, no sex difference (reviewed). (zeng2014epidermalgrowthfactor pages 2-2, zeng2014epidermalgrowthfactor pages 2-4)
Expression discordance: submaxillary:kidney protein ~2000:1 vs mRNA ~2:1; male:female submaxillary mRNA ~10:1. (scott1985thestructureand pages 4-7)
Urinary proEGF bands: ~165, 116, 97, 66, 56 kDa; mature 6 kDa not detected in those assays. (lakshmanan1990identificationofproepidermal pages 1-3)
EGFR ligand affinity (2024): high-affinity ligands including EGF, apparent Kd 0.1–1 nM. (deguchi2024lowaffinityligandsof pages 1-4)
EGFR signaling (2024 seizure model): pERK1/2 ~8-fold at 1.5 h, ~10–20-fold later; EGFR ~15-fold at 72 h (P=0.043). (pastoralonso2024hbegfactivatesegfr pages 1-2)
EGF overexpression phenotype: birth weight ~50% of normal; adult ~80% of normal weight. (chan2000expressionofepidermal pages 1-2)

11) Limitations and evidence gaps (important for annotation)

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)

Key source URLs and publication dates (as available in retrieved texts)

Scott et al., 1985-02. J Cell Sci (Supplement). https://doi.org/10.1242/jcs.1985.supplement_3.3 (scott1985thestructureand pages 1-4)
Zeng & Harris, 2014-04. Seminars in Cell & Developmental Biology. https://doi.org/10.1016/j.semcdb.2014.01.011 (zeng2014epidermalgrowthfactor pages 2-4)
Lakshmanan et al., 1990-12. Biochem Biophys Res Commun. https://doi.org/10.1016/S0006-291X(05)80871-X (lakshmanan1990identificationofproepidermal pages 1-3)
Luetteke et al., 1999-06. Development. https://doi.org/10.1242/dev.126.12.2739 (luetteke1999targetedinactivationof pages 1-2)
Chan & Wong, 2000-12-08 (online 2000-09-22). J Biol Chem. https://doi.org/10.1074/jbc.M004189200 (chan2000expressionofepidermal pages 1-2)
Chen et al., 2017-06. J Biol Chem. https://doi.org/10.1074/jbc.M116.771642 (chen2017thesolubleprotease pages 1-2)
Pastor‑Alonso et al., 2024-07-08. Life Science Alliance. https://doi.org/10.26508/lsa.202201840 (pastoralonso2024hbegfactivatesegfr pages 1-2)
Deguchi et al., 2024-09-26 (preprint posted). bioRxiv. https://doi.org/10.1101/2024.09.25.614853 (deguchi2024lowaffinityligandsof pages 1-4)
Li et al., 2024-01. Meeting abstract. https://doi.org/10.1055/s-0043-1777485 (li2024egfstat1maintainedecm1expression pages 1-5)

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.
(pastoralonso2024hbegfactivatesegfr pages 1-2): Oier Pastor-Alonso, Irene Durá, Sara Bernardo-Castro, Emilio Varea, Teresa Muro-García, Soraya Martín-Suárez, Juan Manuel Encinas-Pérez, and Jose Ramon Pineda. Hb-egf activates egfr to induce reactive neural stem cells in the mouse hippocampus after seizures. Life Science Alliance, 7:e202201840, Jul 2024. URL: https://doi.org/10.26508/lsa.202201840, doi:10.26508/lsa.202201840. This article has 9 citations and is from a peer-reviewed journal.
(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.

Citations

zeng2014epidermalgrowthfactor pages 2-4
zeng2014epidermalgrowthfactor pages 2-2
scott1985thestructureand pages 4-7
lakshmanan1990identificationofproepidermal pages 1-3
chen2017thesolubleprotease pages 1-2
fisher1990metabolismandeffects pages 2-3
luetteke1999targetedinactivationof pages 2-3
chan2000expressionofepidermal pages 1-2
deguchi2024lowaffinityligandsof pages 1-4
pastoralonso2024hbegfactivatesegfr pages 1-2
scott1985thestructureand pages 1-4
luetteke1999targetedinactivationof pages 1-2
sibilia2007theepidermalgrowth pages 2-4
luetteke1999targetedinactivationof pages 6-7
https://doi.org/10.1242/jcs.1985.supplement_3.3
https://doi.org/10.1016/j.semcdb.2014.01.011
https://doi.org/10.1016/S0006-291X(05
https://doi.org/10.1242/dev.126.12.2739
https://doi.org/10.1074/jbc.M004189200
https://doi.org/10.1074/jbc.M116.771642
https://doi.org/10.26508/lsa.202201840
https://doi.org/10.1101/2024.09.25.614853
https://doi.org/10.1055/s-0043-1777485
https://doi.org/10.1242/jcs.1985.supplement_3.3,
https://doi.org/10.1016/j.semcdb.2014.01.011,
https://doi.org/10.1074/jbc.m116.771642,
https://doi.org/10.1016/s0006-291x(05
https://doi.org/10.1210/edrv-11-3-418,
https://doi.org/10.1242/dev.126.12.2739,
https://doi.org/10.1111/j.1432-0436.2007.00238.x,
https://doi.org/10.1074/jbc.m004189200,
https://doi.org/10.1101/2024.09.25.614853,
https://doi.org/10.26508/lsa.202201840,
https://doi.org/10.1055/s-0043-1777485,

📄 View Raw YAML

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: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of MAPK cascade is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: plasma membrane is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008083
    label: growth factor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: growth factor activity is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005154
    label: epidermal growth factor receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: epidermal growth factor receptor binding is directly supported as part of the
      core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: calcium ion binding is biologically plausible for Egf but represents a context-specific
      pathway, localization, interaction, phenotype, or downstream response rather than the
      primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008083
    label: growth factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: growth factor activity is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0010604
    label: positive regulation of macromolecule metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: positive regulation of macromolecule metabolic process is too generic or indirect
      for Egf; the evidence supports a more specific signaling, catalytic, adaptor, or localization
      role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly broad or uninformative relative to the supported core function
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: The annotation captures a real aspect of Egf biology, but membrane is less precise
      than GO:0005886 plasma membrane for this gene.
    action: MODIFY
    reason: Use a more specific GO term supported by the gene product role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048513
    label: animal organ development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: animal organ development is too generic or indirect for Egf; the evidence supports
      a more specific signaling, catalytic, adaptor, or localization role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly broad or uninformative relative to the supported core function
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048731
    label: system development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: system development is too generic or indirect for Egf; the evidence supports
      a more specific signaling, catalytic, adaptor, or localization role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly broad or uninformative relative to the supported core function
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0051049
    label: regulation of transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: regulation of transport is too generic or indirect for Egf; the evidence supports
      a more specific signaling, catalytic, adaptor, or localization role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly broad or uninformative relative to the supported core function
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0071944
    label: cell periphery
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: The annotation captures a real aspect of Egf biology, but cell periphery is less
      precise than GO:0005886 plasma membrane for this gene.
    action: MODIFY
    reason: Use a more specific GO term supported by the gene product role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0080090
    label: regulation of primary metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: regulation of primary metabolic process is too generic or indirect for Egf; the
      evidence supports a more specific signaling, catalytic, adaptor, or localization role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly broad or uninformative relative to the supported core function
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0001525
    label: angiogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: angiogenesis is biologically plausible for Egf but represents a context-specific
      pathway, localization, interaction, phenotype, or downstream response rather than the
      primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0001938
    label: positive regulation of endothelial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of endothelial cell proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0002092
    label: positive regulation of receptor internalization
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of receptor internalization is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005085
    label: guanyl-nucleotide exchange factor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: EGF is a receptor ligand and growth factor; it has no guanine-nucleotide exchange
      factor domain or catalytic GEF role.
    action: REMOVE
    reason: Annotation conflicts with known molecular function or domain architecture
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008083
    label: growth factor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: growth factor activity is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0010595
    label: positive regulation of endothelial cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of endothelial cell migration is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of gene expression is biologically plausible for Egf but
      represents a context-specific pathway, localization, interaction, phenotype, or downstream
      response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0010800
    label: positive regulation of peptidyl-threonine phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of peptidyl-threonine phosphorylation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cell migration is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0042327
    label: positive regulation of phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of phosphorylation is biologically plausible for Egf but
      represents a context-specific pathway, localization, interaction, phenotype, or downstream
      response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of MAPK cascade is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0045840
    label: positive regulation of mitotic nuclear division
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of mitotic nuclear division is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of DNA-templated transcription is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0051048
    label: negative regulation of secretion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of secretion is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- 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: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction is biologically plausible for Egf but represents a context-specific pathway,
      localization, interaction, phenotype, or downstream response rather than the primary
      core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: extracellular exosome is biologically plausible for Egf but represents a context-specific
      pathway, localization, interaction, phenotype, or downstream response rather than the
      primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0070371
    label: ERK1 and ERK2 cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ERK1 and ERK2 cascade is biologically plausible for Egf but represents a context-specific
      pathway, localization, interaction, phenotype, or downstream response rather than the
      primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of canonical Wnt signaling pathway is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0090279
    label: regulation of calcium ion import
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of calcium ion import is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:1900127
    label: positive regulation of hyaluronan biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of hyaluronan biosynthetic process is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:1902966
    label: positive regulation of protein localization to early endosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of protein localization to early endosome is biologically
      plausible for Egf but represents a context-specific pathway, localization, interaction,
      phenotype, or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:1905278
    label: positive regulation of epithelial tube formation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of epithelial tube formation is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:2000008
    label: regulation of protein localization to cell surface
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of protein localization to cell surface is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0001525
    label: angiogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: angiogenesis is biologically plausible for Egf but represents a context-specific
      pathway, localization, interaction, phenotype, or downstream response rather than the
      primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0001938
    label: positive regulation of endothelial cell proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of endothelial cell proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0002092
    label: positive regulation of receptor internalization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of receptor internalization is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005085
    label: guanyl-nucleotide exchange factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: EGF is a receptor ligand and growth factor; it has no guanine-nucleotide exchange
      factor domain or catalytic GEF role.
    action: REMOVE
    reason: Annotation conflicts with known molecular function or domain architecture
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0010595
    label: positive regulation of endothelial cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of endothelial cell migration is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of gene expression is biologically plausible for Egf but
      represents a context-specific pathway, localization, interaction, phenotype, or downstream
      response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0030297
    label: transmembrane receptor protein tyrosine kinase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: transmembrane receptor protein tyrosine kinase activator activity is directly
      supported as part of the core molecular function, direct pathway role, or primary localization
      of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of cell migration is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ERBB2-EGFR signaling pathway is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0042327
    label: positive regulation of phosphorylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of phosphorylation is biologically plausible for Egf but
      represents a context-specific pathway, localization, interaction, phenotype, or downstream
      response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: positive regulation of MAPK cascade is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0045840
    label: positive regulation of mitotic nuclear division
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of mitotic nuclear division is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of DNA-templated transcription is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: receptor ligand activity is directly supported as part of the core molecular
      function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0051048
    label: negative regulation of secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of secretion is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- 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: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction is biologically plausible for Egf but represents a context-specific pathway,
      localization, interaction, phenotype, or downstream response rather than the primary
      core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: extracellular exosome is biologically plausible for Egf but represents a context-specific
      pathway, localization, interaction, phenotype, or downstream response rather than the
      primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0070371
    label: ERK1 and ERK2 cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ERK1 and ERK2 cascade is biologically plausible for Egf but represents a context-specific
      pathway, localization, interaction, phenotype, or downstream response rather than the
      primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of canonical Wnt signaling pathway is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0090279
    label: regulation of calcium ion import
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of calcium ion import is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:1900127
    label: positive regulation of hyaluronan biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of hyaluronan biosynthetic process is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:1902966
    label: positive regulation of protein localization to early endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of protein localization to early endosome is biologically
      plausible for Egf but represents a context-specific pathway, localization, interaction,
      phenotype, or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:1905278
    label: positive regulation of epithelial tube formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of epithelial tube formation is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:2000008
    label: regulation of protein localization to cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of protein localization to cell surface is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005154
    label: epidermal growth factor receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: epidermal growth factor receptor binding is directly supported as part of the
      core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of fibroblast proliferation is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of ERK1 and ERK2 cascade is biologically plausible for Egf
      but represents a context-specific pathway, localization, interaction, phenotype, or
      downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:2000573
    label: positive regulation of DNA biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of DNA biosynthetic process is biologically plausible for
      Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0030297
    label: transmembrane receptor protein tyrosine kinase activator activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: transmembrane receptor protein tyrosine kinase activator activity is directly
      supported as part of the core molecular function, direct pathway role, or primary localization
      of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of MAPK cascade is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:11823423
  review:
    summary: receptor ligand activity is directly supported as part of the core molecular
      function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:11823423
      supporting_text: A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils
        a role for Grb2 in negative signaling.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:14627991
  review:
    summary: receptor ligand activity is directly supported as part of the core molecular
      function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:14627991
      supporting_text: Serine mutations that abrogate ligand-induced ubiquitination and internalization
        of the EGF receptor do not affect c-Cbl association with the receptor.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IDA
  original_reference_id: PMID:12761849
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:12761849
      supporting_text: EGF-stimulated signaling by means of PI3K, PLCgamma1, and PKC isozymes
        regulates branching morphogenesis of the fetal mouse submandibular gland.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:12761849
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:12761849
      supporting_text: EGF-stimulated signaling by means of PI3K, PLCgamma1, and PKC isozymes
        regulates branching morphogenesis of the fetal mouse submandibular gland.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:9529375
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:9529375
      supporting_text: Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse
        embryonic fibroblasts.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:12761849
  review:
    summary: receptor ligand activity is directly supported as part of the core molecular
      function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:12761849
      supporting_text: EGF-stimulated signaling by means of PI3K, PLCgamma1, and PKC isozymes
        regulates branching morphogenesis of the fetal mouse submandibular gland.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:9529375
  review:
    summary: receptor ligand activity is directly supported as part of the core molecular
      function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:9529375
      supporting_text: Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse
        embryonic fibroblasts.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: ISO
  original_reference_id: PMID:11336639
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:11336639
      supporting_text: Heterodimerization of the epidermal-growth-factor (EGF) receptor and
        ErbB2 and the affinity of EGF binding are regulated by different mechanisms.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IDA
  original_reference_id: PMID:22822073
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:22822073
      supporting_text: 2012 Jul 20. Quantitation of the effect of ErbB2 on epidermal growth
        factor receptor binding and dimerization.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IDA
  original_reference_id: PMID:6248866
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:6248866
      supporting_text: Detection of epidermal growth factor-urogastrone and its receptor during
        fetal mouse development.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IDA
  original_reference_id: PMID:7752576
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:7752576
      supporting_text: Tyrosine kinase activity of the EGF receptor in murine metanephric
        organ culture.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: ISO
  original_reference_id: PMID:11336639
  review:
    summary: ERBB2-EGFR signaling pathway is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:11336639
      supporting_text: Heterodimerization of the epidermal-growth-factor (EGF) receptor and
        ErbB2 and the affinity of EGF binding are regulated by different mechanisms.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0038134
    label: ERBB2-EGFR signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:22822073
  review:
    summary: ERBB2-EGFR signaling pathway is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:22822073
      supporting_text: 2012 Jul 20. Quantitation of the effect of ErbB2 on epidermal growth
        factor receptor binding and dimerization.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: ISO
  original_reference_id: PMID:11336639
  review:
    summary: receptor ligand activity is directly supported as part of the core molecular
      function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:11336639
      supporting_text: Heterodimerization of the epidermal-growth-factor (EGF) receptor and
        ErbB2 and the affinity of EGF binding are regulated by different mechanisms.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:22822073
  review:
    summary: receptor ligand activity is directly supported as part of the core molecular
      function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:22822073
      supporting_text: 2012 Jul 20. Quantitation of the effect of ErbB2 on epidermal growth
        factor receptor binding and dimerization.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:6248866
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:6248866
      supporting_text: Detection of epidermal growth factor-urogastrone and its receptor during
        fetal mouse development.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:7752576
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:7752576
      supporting_text: Tyrosine kinase activity of the EGF receptor in murine metanephric
        organ culture.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:6248866
  review:
    summary: receptor ligand activity is directly supported as part of the core molecular
      function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:6248866
      supporting_text: Detection of epidermal growth factor-urogastrone and its receptor during
        fetal mouse development.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:7752576
  review:
    summary: receptor ligand activity is directly supported as part of the core molecular
      function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:7752576
      supporting_text: Tyrosine kinase activity of the EGF receptor in murine metanephric
        organ culture.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IDA
  original_reference_id: PMID:16339969
  review:
    summary: positive regulation of MAPK cascade is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:16339969
      supporting_text: Efficient suppression of FGF-2-induced ERK activation by the cooperative
        interaction among mammalian Sprouty isoforms.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IDA
  original_reference_id: PMID:9030684
  review:
    summary: positive regulation of MAPK cascade is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:9030684
      supporting_text: Mutation in Sos1 dominantly enhances a weak allele of the EGFR, demonstrating
        a requirement for Sos1 in EGFR signaling and development.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:8702723
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:8702723
      supporting_text: 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.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005154
    label: epidermal growth factor receptor binding
  evidence_type: IDA
  original_reference_id: PMID:7678348
  review:
    summary: epidermal growth factor receptor binding is directly supported as part of the
      core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:7678348
      supporting_text: Expression of the epidermal growth factor receptor gene is regulated
        in mouse blastocysts during delayed implantation.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0061098
    label: positive regulation of protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:7678348
  review:
    summary: positive regulation of protein tyrosine kinase activity is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:7678348
      supporting_text: Expression of the epidermal growth factor receptor gene is regulated
        in mouse blastocysts during delayed implantation.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0050731
    label: positive regulation of peptidyl-tyrosine phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:21186272
  review:
    summary: positive regulation of peptidyl-tyrosine phosphorylation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:21186272
      supporting_text: Activation of the neuregulin/ErbB system during physiological ventricular
        remodeling in pregnancy.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0043388
    label: positive regulation of DNA binding
  evidence_type: IDA
  original_reference_id: PMID:15156153
  review:
    summary: positive regulation of DNA binding is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:15156153
      supporting_text: Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT
        signalling.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0046425
    label: regulation of receptor signaling pathway via JAK-STAT
  evidence_type: IDA
  original_reference_id: PMID:15156153
  review:
    summary: regulation of receptor signaling pathway via JAK-STAT is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:15156153
      supporting_text: Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT
        signalling.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0090370
    label: negative regulation of cholesterol efflux
  evidence_type: IDA
  original_reference_id: PMID:20037141
  review:
    summary: negative regulation of cholesterol efflux is biologically plausible for Egf but
      represents a context-specific pathway, localization, interaction, phenotype, or downstream
      response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:20037141
      supporting_text: 2009 Dec 25. Inhibition of ERK1/2 and activation of liver X receptor
        synergistically induce macrophage ABCA1 expression and cholesterol efflux.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:2000060
    label: positive regulation of ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:20208556
  review:
    summary: positive regulation of ubiquitin-dependent protein catabolic process is biologically
      plausible for Egf but represents a context-specific pathway, localization, interaction,
      phenotype, or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:20208556
      supporting_text: Presenilin modulates EGFR signaling and cell transformation by regulating
        the ubiquitin ligase Fbw7.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0051223
    label: regulation of protein transport
  evidence_type: ISO
  original_reference_id: PMID:19723622
  review:
    summary: regulation of protein transport is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:19723622
      supporting_text: '2009 Sep 1. Activator of G protein signaling 8 (AGS8) is required
        for hypoxia-induced apoptosis of cardiomyocytes: role of G betagamma and connexin
        43 (CX43).'
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17626015
  review:
    summary: protein binding is too generic or indirect for Egf; the evidence supports a more
      specific signaling, catalytic, adaptor, or localization role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly broad or uninformative relative to the supported core function
    supported_by:
    - reference_id: PMID:17626015
      supporting_text: 2007 Jul 10. SGIP1alpha is an endocytic protein that directly interacts
        with phospholipids and Eps15.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:17626015
  review:
    summary: plasma membrane is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:17626015
      supporting_text: 2007 Jul 10. SGIP1alpha is an endocytic protein that directly interacts
        with phospholipids and Eps15.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008083
    label: growth factor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: growth factor activity is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005154
    label: epidermal growth factor receptor binding
  evidence_type: IDA
  original_reference_id: PMID:6315706
  review:
    summary: epidermal growth factor receptor binding is directly supported as part of the
      core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:6315706
      supporting_text: Epidermal growth factor-like transforming growth factor.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:6315706
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:6315706
      supporting_text: Epidermal growth factor-like transforming growth factor.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0060749
    label: mammary gland alveolus development
  evidence_type: IGI
  original_reference_id: PMID:10331984
  review:
    summary: mammary gland alveolus development is biologically plausible for Egf but represents
      a context-specific pathway, localization, interaction, phenotype, or downstream response
      rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:10331984
      supporting_text: Targeted inactivation of the EGF and amphiregulin genes reveals distinct
        roles for EGF receptor ligands in mouse mammary gland development.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-179883
  review:
    summary: extracellular region is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-179883
  review:
    summary: plasma membrane is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IDA
  original_reference_id: PMID:7641815
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:7641815
      supporting_text: Altering the expression of cell surface beta 1,4-galactosyltransferase
        modulates cell growth.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:7641815
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:7641815
      supporting_text: Altering the expression of cell surface beta 1,4-galactosyltransferase
        modulates cell growth.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:7641815
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:7641815
      supporting_text: Altering the expression of cell surface beta 1,4-galactosyltransferase
        modulates cell growth.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0021940
    label: positive regulation of cerebellar granule cell precursor proliferation
  evidence_type: IDA
  original_reference_id: PMID:10027293
  review:
    summary: The cited Sonic Hedgehog paper does not support an Egf annotation.
    action: REMOVE
    reason: PMID:10027293 supports Sonic Hedgehog-driven cerebellar granule cell precursor
      proliferation, not an EGF/Egf role in this process.
    supported_by:
    - reference_id: PMID:10027293
      supporting_text: Control of neuronal precursor proliferation in the cerebellum by Sonic
        Hedgehog.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:15051883
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:15051883
      supporting_text: Neuropoietin, a new IL-6-related cytokine signaling through the ciliary
        neurotrophic factor receptor.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0048754
    label: branching morphogenesis of an epithelial tube
  evidence_type: IDA
  original_reference_id: PMID:15831470
  review:
    summary: The cited BMP7/ILK paper does not support an Egf annotation.
    action: REMOVE
    reason: PMID:15831470 describes BMP7-dependent renal epithelial morphogenesis mediated
      by ILK/p38 and does not provide evidence for an EGF/Egf role in epithelial tube
      branching morphogenesis.
    supported_by:
    - reference_id: PMID:15831470
      supporting_text: Integrin-linked kinase mediates bone morphogenetic protein 7-dependent
        renal epithelial cell morphogenesis.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:15695332
  review:
    summary: epidermal growth factor receptor signaling pathway is directly supported as part
      of the core molecular function, direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:15695332
      supporting_text: Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator
        of epidermal growth factor signaling.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:15695332
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:15695332
      supporting_text: Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator
        of epidermal growth factor signaling.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:14712229
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:14712229
      supporting_text: 'G-protein-coupled receptor-mediated activation of rap GTPases: characterization
        of a novel Galphai regulated pathway.'
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:15509736
  review:
    summary: positive regulation of cell population proliferation is biologically plausible
      for Egf but represents a context-specific pathway, localization, interaction, phenotype,
      or downstream response rather than the primary core function.
    action: KEEP_AS_NON_CORE
    reason: Supported secondary or context-specific role
    supported_by:
    - reference_id: PMID:15509736
      supporting_text: Fibroblast growth factor receptor signaling promotes radial glial identity
        and interacts with Notch1 signaling in telencephalic progenitors.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IDA
  original_reference_id: PMID:8240367
  review:
    summary: extracellular space is directly supported as part of the core molecular function,
      direct pathway role, or primary localization of Egf.
    action: ACCEPT
    reason: Directly supported core function, process, or location
    supported_by:
    - reference_id: PMID:8240367
      supporting_text: An inborn error in epidermal growth factor prohormone metabolism in
        a mouse model of autosomal recessive polycystic kidney disease.
    - 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: Falcon deep research report reviewed for GO term specificity, core-function
        context, and evidence synthesis.
- term:
    id: GO:0018108
    label: peptidyl-tyrosine phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:14561752
  review:
    summary: The cited GnT-V/cadherin paper does not support an Egf-specific phosphorylation
      annotation.
    action: REMOVE
    reason: PMID:14561752 describes N-acetylglucosaminyltransferase V effects on
      cadherin-associated adhesion and signaling, not direct EGF/Egf-specific positive
      regulation of peptidyl-tyrosine phosphorylation.
    supported_by:
    - reference_id: PMID:14561752
      supporting_text: 2003 Oct 15. N-acetylglucosaminyltransferase V expression levels regulate
        cadherin-associated homotypic cell-cell adhesion and intracellular signaling pathways.
- term:
    id: GO:0050730
    label: regulation of peptidyl-tyrosine phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:11940581
  review:
    summary: The cited PDGF/Gab1 paper is not specific enough to support an Egf annotation.
    action: REMOVE
    reason: PMID:11940581 shows Gab1 tyrosine phosphorylation after EGF and PDGF
      stimulation in vascular smooth muscle cells, but the central mechanism analyzed is
      PDGF/PLCgamma/PKC-dependent Gab1 phosphorylation and is not suitable evidence for
      an Egf-specific GO annotation.
    supported_by:
    - reference_id: PMID:11940581
      supporting_text: 2002 Apr 8. 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.
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:0005615
    label: extracellular space
  - 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: Falcon deep research report reviewed for GO term specificity, core-function
      context, and evidence synthesis.
- 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:0005615
    label: extracellular space
  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: Falcon deep research report reviewed for GO term specificity, core-function
      context, and evidence synthesis.
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []

Egf

Gene Description

Existing Annotations Review

Core Functions

Processed EGF binds and activates EGFR-family receptors, promoting receptor dimerization and tyrosine kinase signaling.

EGF directly engages EGFR to trigger receptor activation and downstream signal transduction.

References

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Research report: Mouse Egf (UniProt P01132) — functional annotation of pro-epidermal growth factor (proEGF)

Scope and target verification

1) Key concepts and definitions (current understanding)

1.1 What “Egf” encodes: a membrane-anchored ligand precursor

1.2 “Processing/shedding” of EGFR ligands

1.3 Molecular function: EGFR ligand activity

2) Protein architecture and subcellular localization

2.1 Architecture

2.2 Localization: membrane association and tissue-specific compartments

3) Expression patterns (where Egf is made)

3.1 Major sites of expression

3.2 Sex dimorphism

4) Biogenesis and processing: mature EGF vs high-molecular-weight forms

4.1 Salivary gland processing and regulated release

4.2 Kidney: high mRNA but limited mature EGF, with urinary proEGF species

4.3 Context-specific proteolysis: platelet proEGF cleavage as a mechanistic example

5) Signaling pathways and biochemical roles

5.1 Canonical EGFR signaling pathways downstream of EGF

5.2 Kidney functional interpretation: ion transport hypothesis

6) In vivo genetics and phenotypes (mouse)

6.1 Egf loss-of-function is mild, indicating redundancy among EGFR ligands

6.2 Combinatorial ligand loss unmasks roles in mammary gland differentiation and neonatal survival

6.3 EGF overexpression is sufficient to cause growth defects

7) Recent developments (prioritizing 2023–2024)

7.1 2024: EGFR ligand affinity and long-range signaling in epithelia (wound repair context)

7.2 2024: EGFR signaling in the adult hippocampal niche after seizures (ligand context: HB-EGF)

7.3 2024: Proposed EGF/EGFR→STAT1 control of hepatocyte ECM1 (conference abstract)

8) Current applications and real-world implementations

9) Expert synthesis and interpretation (authoritative viewpoints)

10) Key quantitative/statistical highlights (selected)

11) Limitations and evidence gaps (important for annotation)

Key source URLs and publication dates (as available in retrieved texts)

Citations

📄 View Raw YAML