FGFR2 (Fibroblast Growth Factor Receptor 2) encodes a receptor tyrosine kinase that mediates FGF signaling in development, tissue repair, and homeostasis. CRITICAL ISOFORM BIOLOGY: Alternative splicing of exon IIIb vs IIIc in the third Ig-like domain creates isoforms with MUTUALLY EXCLUSIVE ligand specificities: (1) FGFR2IIIb (P21802-3, KGFR) is expressed in EPITHELIAL cells and binds FGF1, FGF3, FGF7 (KGF), and FGF10. FGF7 and FGF10 bind ONLY to IIIb. (2) FGFR2IIIc (P21802-1, BEK) is expressed in MESENCHYMAL cells and binds FGF1, FGF2, FGF4, FGF6, and FGF9. FGF2 binds preferentially to IIIc. This isoform switching enables PARACRINE signaling between epithelium and mesenchyme: mesenchyme produces FGF7/10 to signal to epithelial IIIb, while epithelium produces FGF2/4 to signal to mesenchymal IIIc. Critical for limb development, lung branching morphogenesis, and wound healing. Additional isoforms: Secreted/soluble forms (P21802-14, P21802-19) may act as decoy receptors. Numerous other splice variants exist with various domain combinations. Cancer relevance: IIIb-to-IIIc isoform switching accompanies epithelial-mesenchymal transition (EMT) and correlates with metastatic potential in some cancers.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005007 fibroblast growth factor receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: FGFR2 is unambiguously a fibroblast growth factor receptor. UniProt confirms it is a "Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors." This applies to all transmembrane isoforms (both IIIb/KGFR and IIIc/BEK), though with different ligand specificities. Deep research confirms FGFR2 as a receptor tyrosine kinase whose primary function is transducing FGF signals via autophosphorylation and downstream pathway activation. Reason: Core molecular function of FGFR2. Extensive experimental evidence from multiple studies (PMID:8663044, PMID:16597617, PMID:15629145) demonstrates FGF receptor activity. The IBA annotation appropriately captures the conserved function. Supporting Evidence: UniProtKB:P21802 Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors file:human/FGFR2/FGFR2-deep-research-falcon.md FGFR2 is a member of the FGFR receptor tyrosine kinase family that transduces extracellular fibroblast growth factor (FGF) signals into intracellular phosphorylation-dependent signaling programs that control proliferation, survival, differentiation, and migration. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane localization is confirmed for all transmembrane FGFR2 isoforms (IIIb and IIIc). However, secreted isoforms (P21802-14, P21802-19) are not plasma membrane-localized. The annotation is appropriate at the gene level since most functional isoforms are transmembrane. Reason: UniProt confirms "Cell membrane; Single-pass type I membrane protein" for main isoforms. Extensive localization data supports plasma membrane localization for functional receptor isoforms. Supporting Evidence: UniProtKB:P21802 SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein |
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | ACCEPT | Summary: FGFR2 signaling promotes cell proliferation in keratinocytes and immature osteoblasts. UniProt notes it "Promotes cell proliferation in keratinocytes and immature osteoblasts." This is a well-established downstream effect of FGF signaling through both IIIb and IIIc isoforms. Reason: Core biological process for FGFR2. Multiple studies demonstrate proliferative effects (PMID:8663044, PMID:15629145, PMID:16597617). This applies to both major splice variants with different ligands driving the same outcome. Supporting Evidence: UniProtKB:P21802 Promotes cell proliferation in keratinocytes and immature osteoblasts |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: FGFR2 is a core component of FGF receptor signaling. Ligand binding leads to receptor dimerization, autophosphorylation, and activation of downstream cascades including PLCG1, MAPK, and PI3K/AKT pathways. Reason: Fundamental role of FGFR2. UniProt extensively documents signaling mechanism including phosphorylation of PLCG1, FRS2, and activation of RAS-MAPK and AKT pathways. Both IIIb and IIIc isoforms signal through these pathways. Supporting Evidence: UniProtKB:P21802 Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway |
| GO:0001525 angiogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FGF signaling through FGFRs is known to promote angiogenesis, particularly FGF2 signaling through FGFR2IIIc (mesenchymal isoform). However, this may be more prominent for FGFR1 in endothelial cells. The annotation is reasonable but likely represents a non-core function. Reason: Angiogenesis is documented for FGF/FGFR signaling generally, but FGFR2's primary roles are in epithelial-mesenchymal signaling for organ development rather than vascular biology. This is a secondary rather than core function. |
| GO:0043410 positive regulation of MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: MAPK cascade activation is a core downstream signaling event for FGFR2. UniProt confirms that FRS2 phosphorylation leads to recruitment of GRB2/SOS1 and activation of RAS-MAPK signaling. Reason: Core signaling output of FGFR2. Well-documented in UniProt and multiple publications (PMID:15629145, PMID:17623664). Both IIIb and IIIc isoforms activate MAPK upon ligand binding. Supporting Evidence: UniProtKB:P21802 mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway |
| GO:0043235 receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: FGFR2 forms homodimers upon ligand binding and also forms complexes with heparan sulfate proteoglycan co-receptors. UniProt confirms "Homodimer after ligand binding." Reason: FGFR2 functions as part of a receptor complex including FGF ligands, heparan sulfate, and in some cases KLB (for FGF19/21). Dimerization is required for receptor activation. Supporting Evidence: UniProtKB:P21802 Monomer. Homodimer after ligand binding. |
| GO:0017134 fibroblast growth factor binding | IBA GO_REF:0000033 | ACCEPT | Summary: FGFR2 binds multiple FGFs with isoform-specific preferences. IIIc (P21802-1) has high affinity for FGF1, FGF2; IIIb (P21802-3) has high affinity for FGF1, FGF7. CRITICAL ISOFORM NOTE - FGF7 binds ONLY to IIIb (epithelial); FGF2 binds preferentially to IIIc (mesenchymal). Reason: Core molecular function. Extensive structural and biochemical data (PMID:8663044, PMID:10830168, PMID:12591959) document FGF binding. The annotation at gene level is appropriate though ligand specificity differs by isoform. Supporting Evidence: UniProtKB:P21802 Isoform 1 has high affinity for FGF1 and FGF2, but low affinity for FGF7. Isoform 3 has high affinity for FGF1 and FGF7 |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: FGFR2 is a tyrosine kinase that binds ATP for its catalytic activity. Nucleotide binding is accurate but overly general - ATP binding is more specific. Reason: True but general. FGFR2 has a kinase domain that binds ATP. The more specific term "ATP binding" is also annotated and preferred. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: FGFR2 is a protein kinase. The annotation is correct but "protein tyrosine kinase activity" is more specific and preferred. Reason: Correct parent term. FGFR2 has documented kinase activity (EC 2.7.10.1). More specific child term annotations also exist. |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: FGFR2 is a receptor tyrosine kinase that autophosphorylates and phosphorylates substrates including PLCG1, FRS2, and PAK4 on tyrosine residues. Reason: Core molecular function. UniProt confirms EC 2.7.10.1 classification and documents phosphorylation of multiple substrates. Applies to all kinase- containing isoforms. Supporting Evidence: UniProtKB:P21802 Phosphorylates PLCG1, FRS2 and PAK4 |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: FGFR2 is a single-pass type I transmembrane receptor tyrosine kinase. This is the most specific and appropriate molecular function term for membrane- bound isoforms. Reason: Most specific appropriate MF term for transmembrane FGFR2 isoforms. Note that secreted isoforms (P21802-14, P21802-19) lack transmembrane domain and kinase activity. |
| GO:0005007 fibroblast growth factor receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. FGFR2 is unambiguously an FGF receptor. Reason: Core function - duplicates IBA annotation with different evidence. Correct. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: FGFR2 kinase domain binds ATP. Crystal structures confirm ATP binding (PDB entries with ATP analogs). Reason: Core function for kinase activity. Structural data confirms ATP binding site. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: The secreted/soluble isoforms (P21802-14 soluble KGFR, P21802-19 soluble KGFR) are found in the extracellular region. For transmembrane isoforms, the N-terminal region including Ig-like domains is extracellular. Reason: Appropriate for secreted isoforms. UniProt confirms isoforms 8 (K-sam-IV, Soluble KGFR) and 13 (Soluble KGFR) are secreted forms that would localize to the extracellular region. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | ACCEPT | Summary: FGFR2 is N-glycosylated and transits through the Golgi. UniProt notes "N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus." Reason: FGFR2 passes through Golgi during maturation. Also documented as "Golgi apparatus" in subcellular location. Represents trafficking intermediate. Supporting Evidence: UniProtKB:P21802 SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Golgi apparatus. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Duplicate of IBA annotation. Plasma membrane localization for transmembrane isoforms is well established. Reason: Correct - duplicates IBA with different evidence. |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: FGFR2 has complex effects on apoptosis - it can promote apoptosis in differentiated osteoblasts but inhibit it in keratinocytes and immature osteoblasts. The UniProt keyword may be too general. Reason: UniProt notes FGFR2 "promotes apoptosis in differentiated osteoblasts" but this is context-dependent and not a primary function. The annotation is valid but represents a secondary/context-specific role. Supporting Evidence: UniProtKB:P21802 Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts |
| GO:0008201 heparin binding | IEA GO_REF:0000043 | ACCEPT | Summary: FGFR2 binds heparan sulfate glycosaminoglycans which serve as coreceptors. Heparin (a highly sulfated heparan sulfate) is used experimentally. Reason: Documented function. UniProt confirms "Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors." Crystal structures show heparin binding (PMID:11069186). Supporting Evidence: UniProtKB:P21802 Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. FGFR2 promotes cell proliferation. Reason: Correct - duplicates IBA with different evidence. |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. FGFR2 is a core component of FGF signaling. Reason: Correct - duplicates IBA with different evidence. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Transmembrane FGFR2 isoforms are integral membrane proteins. This is a parent term of plasma membrane - overly general but not wrong. Reason: Correct but general. More specific annotations (plasma membrane) exist. |
| GO:0016301 kinase activity | IEA GO_REF:0000043 | ACCEPT | Summary: FGFR2 has kinase activity. This is a parent of the more specific protein tyrosine kinase activity annotations. Reason: Correct but overly general. More specific annotations exist. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Kinases are transferases (transfer phosphate groups). This is very general but technically correct. Reason: Correct parent term. Very general but valid. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000120 | ACCEPT | Summary: FGFR2 is found in cytoplasmic vesicles during internalization after ligand binding. UniProt notes "After ligand binding, the activated receptor is rapidly internalized and degraded." Reason: Valid location during receptor trafficking/internalization. Supporting Evidence: UniProtKB:P21802 After ligand binding, the activated receptor is rapidly internalized and degraded |
| GO:0033688 regulation of osteoblast proliferation | IEA GO_REF:0000117 | ACCEPT | Summary: FGFR2 regulates osteoblast proliferation - it promotes proliferation in immature osteoblasts. This is relevant to craniosynostosis syndromes caused by FGFR2 mutations. Reason: UniProt confirms FGFR2 "Promotes cell proliferation in keratinocytes and immature osteoblasts" and "Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis." |
| GO:0043009 chordate embryonic development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: FGFR2 is required for normal embryonic development. UniProt confirms it is "Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development." Reason: Valid but very general developmental term. More specific developmental processes (limb, lung, skeleton) are better descriptors of FGFR2 function. |
| GO:0043410 positive regulation of MAPK cascade | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate annotation (IBA already reviewed). MAPK cascade activation is a core downstream signaling output of FGFR2. Reason: Duplicates IBA with different evidence. Core signaling function. |
| GO:0045595 regulation of cell differentiation | IEA GO_REF:0000117 | ACCEPT | Summary: FGFR2 regulates differentiation of multiple cell types including osteoblasts, keratinocytes, and epithelial cells. This is a core function. Reason: UniProt confirms role in "regulation of cell proliferation, differentiation, migration and apoptosis." Applies to both IIIb (epithelial differentiation) and IIIc (mesenchymal differentiation) isoforms. |
| GO:0048562 embryonic organ morphogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: FGFR2 is required for morphogenesis of multiple embryonic organs including limbs, lungs, and craniofacial structures. UniProt confirms it is "Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development." Reason: Core developmental function. FGFR2 is essential for morphogenesis of multiple organs through epithelial-mesenchymal interactions. Consistent with ISS annotation for the same term. Supporting Evidence: UniProtKB:P21802 Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development |
| GO:0048705 skeletal system morphogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: FGFR2 is critical for skeletal development. Mutations cause multiple craniosynostosis syndromes (Crouzon, Apert, Pfeiffer, Jackson-Weiss). Reason: UniProt confirms "required for normal skeleton development" and documents multiple skeletal disorder phenotypes from FGFR2 mutations. |
| GO:1904888 cranial skeletal system development | IEA GO_REF:0000117 | ACCEPT | Summary: FGFR2 is critical for cranial skeleton development. Mutations cause craniosynostosis - premature fusion of cranial sutures. Reason: Strong evidence from human genetics - FGFR2 mutations cause Crouzon syndrome, Apert syndrome, Pfeiffer syndrome, and other craniosynostoses. |
| GO:0005515 protein binding | IPI PMID:10618369 Structural interactions of fibroblast growth factor receptor... | MODIFY | Summary: PMID:10618369 is a structural study of FGFR2-FGF1 complex. The term "protein binding" is uninformative - more specific terms like "fibroblast growth factor binding" are available and preferred. Reason: "Protein binding" is too generic for GO annotation. This paper documents FGF binding which is already captured by GO:0017134. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:10618369 Structural interactions of fibroblast growth factor receptor with its ligands. |
| GO:0005515 protein binding | IPI PMID:10830168 Crystal structures of two FGF-FGFR complexes reveal the dete... | MODIFY | Summary: PMID:10830168 reports crystal structures of FGF-FGFR complexes. Shows determinants of ligand-receptor specificity. "Protein binding" is too generic. Reason: Paper specifically documents FGF binding. Should use GO:0017134 fibroblast growth factor binding instead. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:10830168 Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. |
| GO:0005515 protein binding | IPI PMID:11390973 Structural basis for fibroblast growth factor receptor 2 act... | MODIFY | Summary: PMID:11390973 describes structural basis for FGFR2 activation in Apert syndrome, examining FGF2 binding. "Protein binding" is too generic. Reason: Paper documents FGF2 binding to FGFR2. Should use more specific term. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:11390973 Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome. |
| GO:0005515 protein binding | IPI PMID:12591959 Structural basis by which alternative splicing confers speci... | MODIFY | Summary: PMID:12591959 examines structural basis by which alternative splicing confers specificity in FGF receptors. Shows FGF10 binding to FGFR2IIIb. Reason: Paper documents isoform-specific FGF binding. Should use GO:0017134. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:12591959 Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors. |
| GO:0005515 protein binding | IPI PMID:1309608 Determination of ligand-binding specificity by alternative s... | MODIFY | Summary: PMID:1309608 is a seminal paper showing that alternative splicing creates two distinct growth factor receptors with different ligand specificities. Documents FGF1 and FGF7 binding differences between isoforms. Reason: Classic paper on FGFR2 isoform-specific FGF binding. Should use GO:0017134. Proposed replacements: fibroblast growth factor binding Supporting Evidence: PMID:1309608 Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene. |
| GO:0005515 protein binding | IPI PMID:22726438 Inhibition of basal FGF receptor signaling by dimeric Grb2. | MODIFY | Summary: PMID:22726438 documents inhibition of basal FGF receptor signaling by dimeric Grb2. Shows GRB2 interaction with FGFR2. Reason: Documents specific GRB2 binding. Should be annotated with a more specific term reflecting signaling adaptor interaction. Proposed replacements: transmembrane receptor protein tyrosine kinase adaptor activity Supporting Evidence: PMID:22726438 Inhibition of basal FGF receptor signaling by dimeric Grb2. |
| GO:0005515 protein binding | IPI PMID:23597563 Molecular mechanism of SSR128129E, an extracellularly acting... | MARK AS OVER ANNOTATED | Summary: PMID:23597563 describes molecular mechanism of SSR128129E, an extracellularly acting small-molecule allosteric inhibitor. Documents drug-receptor interaction. Reason: This paper is about drug binding, not protein-protein interaction. The "protein binding" annotation does not capture meaningful biology here. Supporting Evidence: PMID:23597563 Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MARK AS OVER ANNOTATED | Summary: PMID:25241761 uses in situ proximity ligation assay to profile endogenous protein-protein interactions. High-throughput interactome study. Reason: High-throughput study without specific functional characterization. "Protein binding" is too generic to be informative. Supporting Evidence: PMID:25241761 Oct 9. Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. |
| GO:0005515 protein binding | IPI PMID:26267536 Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for... | MARK AS OVER ANNOTATED | Summary: PMID:26267536 describes long-pentraxin 3 derivative as FGF trap for cancer therapy. Documents FGF sequestration rather than receptor binding. Reason: Paper focuses on therapeutic FGF trapping, not native FGFR2 interactions. "Protein binding" is not informative here. Supporting Evidence: PMID:26267536 Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: PMID:33961781 is a large-scale proteome study of the human interactome. High-throughput data without specific functional characterization. Reason: High-throughput interactome study. "Protein binding" is too generic to be informative for specific gene annotation. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | MARK AS OVER ANNOTATED | Summary: PMID:35384245 is a physical interactome atlas of human receptor tyrosine kinases. Large-scale study of RTK interactions. Reason: High-throughput interactome study. Generic "protein binding" annotations from such studies add little value. Supporting Evidence: PMID:35384245 Physical and functional interactome atlas of human receptor tyrosine kinases. |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MARK AS OVER ANNOTATED | Summary: PMID:35922511 is a physical wiring diagram for the human immune system. Large-scale protein interaction study. Reason: High-throughput study. Generic "protein binding" from such studies is not informative for specific gene function. Supporting Evidence: PMID:35922511 Aug 3. A physical wiring diagram for the human immune system. |
| GO:0001837 epithelial to mesenchymal transition | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ISOFORM-SPECIFIC CONCERN: FGFR2 isoform switching (IIIb to IIIc) is associated with EMT. IIIb is epithelial; IIIc is mesenchymal. This annotation conflates gene-level with isoform-specific biology. Reason: The isoform switch from IIIb to IIIc accompanies EMT in cancer, but FGFR2 itself does not directly cause EMT. This is a correlative rather than causative role. The annotation may be valid but represents secondary biology. |
| GO:0003416 endochondral bone growth | IEA GO_REF:0000107 | ACCEPT | Summary: FGFR2 plays a role in bone development. Mutations cause craniosynostosis and affect skeletal growth. Reason: Valid bone development function supported by disease phenotypes. UniProt documents FGFR2 role in osteogenesis and skeletal development. |
| GO:0009986 cell surface | IEA GO_REF:0000107 | ACCEPT | Summary: FGFR2 is a cell surface receptor. More specific than plasma membrane in indicating the exposed surface. Reason: Valid localization. FGFR2 is a transmembrane receptor exposed at the cell surface for ligand binding. |
| GO:0017134 fibroblast growth factor binding | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. FGF binding is a core FGFR2 function. Reason: Core function - duplicates IBA with different evidence. |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: LPS response is not a characterized FGFR2 function. This annotation may reflect expression changes rather than direct function. Reason: No clear evidence that FGFR2 has a direct role in LPS response. This is likely an ortholog transfer from expression data rather than functional data. |
| GO:0044344 cellular response to fibroblast growth factor stimulus | IEA GO_REF:0000107 | ACCEPT | Summary: FGFR2 mediates cellular response to FGF. This is its core function as an FGF receptor. Reason: Core function. FGFR2 is the receptor that mediates cellular response to multiple FGFs. |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ethanol response is not a characterized FGFR2 function. This annotation likely reflects expression changes rather than direct function. Reason: No evidence that FGFR2 has a direct role in ethanol response. Likely ortholog transfer from expression data. |
| GO:0048333 mesodermal cell differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: FGFR2IIIc (mesenchymal isoform) is involved in mesenchymal/mesodermal cell biology. This annotation may be partially isoform-specific. Reason: Valid for FGFR2IIIc isoform specifically. FGF signaling through IIIc supports mesenchymal cell differentiation. |
| GO:0050680 negative regulation of epithelial cell proliferation | IEA GO_REF:0000120 | UNDECIDED | Summary: This annotation seems contradictory to FGFR2's known role in promoting keratinocyte (epithelial) proliferation. The annotation may be context- specific or erroneous. Reason: UniProt states FGFR2 "promotes cell proliferation in keratinocytes" which contradicts negative regulation. May apply to specific contexts but unclear. |
| GO:0071300 cellular response to retinoic acid | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Retinoic acid response is not a characterized FGFR2 function. May reflect expression regulation rather than functional response. Reason: No clear evidence for direct FGFR2 role in retinoic acid response. Likely ortholog transfer from expression data. |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Hypoxia response is not a well-characterized FGFR2 function. May reflect expression changes in hypoxia. Reason: No clear evidence for direct FGFR2 role in hypoxia response. Likely ortholog transfer from expression data. |
| GO:0071560 cellular response to transforming growth factor beta stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TGF-beta response may involve FGFR2 in certain contexts, especially related to EMT where both pathways interact. Reason: There is crosstalk between FGF and TGF-beta pathways in EMT and development, but this is not a primary FGFR2 function. |
| GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: FGF signaling can promote smooth muscle cell proliferation, potentially via FGFR2IIIc in mesenchymal cells. Reason: Valid but not a primary FGFR2 function. FGF2 signaling through FGFR can promote VSMC proliferation but this is not unique to FGFR2. |
| GO:0009986 cell surface | IDA PMID:17959718 Heparanase cleavage of perlecan heparan sulfate modulates FG... | ACCEPT | Summary: PMID:17959718 examines heparanase cleavage of perlecan and FGF10 activity in submandibular gland branching morphogenesis. Shows FGFR2 at cell surface. Reason: Direct experimental evidence for cell surface localization during FGF10-FGFR2 signaling in branching morphogenesis. Supporting Evidence: PMID:17959718 Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654748 | ACCEPT | Summary: Reactome pathway annotation. Multiple Reactome entries document FGFR2 plasma membrane localization in various signaling contexts. Reason: Plasma membrane localization is well established for transmembrane FGFR2 isoforms. Reactome pathway data supports this. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5655233 | ACCEPT | Summary: Reactome pathway annotation for FGFR2 signaling. Duplicates other PM annotations. Reason: Valid localization, consistent with other evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5655241 | ACCEPT | Summary: Reactome pathway annotation. Part of FGFR2 signaling pathway documentation. Reason: Valid localization, consistent with other evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5655245 | ACCEPT | Summary: Reactome pathway annotation for FGFR2 at plasma membrane. Reason: Valid localization, duplicates other evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5655268 | ACCEPT | Summary: Reactome pathway annotation for FGFR2 signaling. Reason: Valid localization, consistent with established biology. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5655301 | ACCEPT | Summary: Reactome pathway annotation for FGFR2 signaling. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5655320 | ACCEPT | Summary: Reactome pathway annotation for FGFR2 signaling. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5655323 | ACCEPT | Summary: Reactome pathway annotation for FGFR2 signaling. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5655339 | ACCEPT | Summary: Reactome pathway annotation for FGFR2 signaling. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5655343 | ACCEPT | Summary: Reactome pathway annotation for FGFR2 signaling. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8853313 | ACCEPT | Summary: Reactome pathway annotation for FGFR2 fusions autophosphorylation. Documents aberrant signaling in cancer. Reason: Valid localization for wild-type and fusion FGFR2. |
| GO:0010839 negative regulation of keratinocyte proliferation | IMP PMID:21412257 MiR-125b, a microRNA downregulated in psoriasis, modulates k... | REMOVE | Summary: PMID:21412257 shows miR-125b modulates keratinocyte proliferation by targeting FGFR2. Knockdown of FGFR2 by miRNA reduces proliferation, suggesting FGFR2 normally promotes (not inhibits) keratinocyte proliferation. Reason: This annotation appears incorrect. The paper shows that FGFR2 knockdown reduces keratinocyte proliferation, meaning FGFR2 positively regulates proliferation. The annotation should be GO:0050679 (positive regulation of epithelial cell proliferation) rather than negative regulation. Supporting Evidence: PMID:21412257 Mar 17. MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8853319 | ACCEPT | Summary: Reactome pathway annotation for plasma membrane localization. FGFR2 transmembrane isoforms are plasma membrane receptors. Multiple Reactome pathways include FGFR2 at the plasma membrane. Reason: Correct localization for transmembrane FGFR2 isoforms. Duplicate entries from different Reactome pathways reflect FGFR2 participation in multiple signaling contexts at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029989 | ACCEPT | Summary: Reactome pathway annotation duplicate. Plasma membrane localization is well established for transmembrane FGFR2 isoforms. Reason: Duplicate of other plasma membrane annotations from different Reactome pathway contexts. Valid for transmembrane isoforms. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029983 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029984 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2033472 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2033474 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2033479 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2033486 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2033488 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2033490 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2077424 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-109699 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-190413 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2316434 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2400009 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654147 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654157 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654159 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654397 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654399 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654402 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654404 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654406 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654407 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654562 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654603 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654605 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654607 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654608 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654612 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654614 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654615 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654618 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654620 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654622 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654677 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654697 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654701 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5654729 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-190258 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-190260 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-190408 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-8853328 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029988 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2029992 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2067713 | ACCEPT | Summary: Reactome pathway annotation duplicate for plasma membrane localization. Reason: Valid duplicate annotation from different Reactome pathway. |
| GO:0048701 embryonic cranial skeleton morphogenesis | IMP PMID:7874170 Jackson-Weiss and Crouzon syndromes are allelic with mutatio... | ACCEPT | Summary: Mutations in FGFR2 cause Jackson-Weiss and Crouzon syndromes, which feature craniosynostosis (premature fusion of cranial sutures). This demonstrates FGFR2 role in cranial skeleton development. PMID:7874170 identified FGFR2 mutations in the IIIc domain in Jackson-Weiss syndrome families. Reason: Strong genetic evidence linking FGFR2 mutations to craniosynostosis syndromes. FGFR2 is essential for normal cranial suture development; gain-of-function mutations cause premature suture fusion. This is a well-established core developmental function particularly for the IIIc isoform in mesenchyme. Supporting Evidence: PMID:7874170 We now report an FGFR2 mutation in the conserved region of the immunoglobulin IIIc domain in the Jackson-Weiss syndrome family in which the syndrome was originally described. |
| GO:0048701 embryonic cranial skeleton morphogenesis | IMP PMID:7987400 Mutations in the fibroblast growth factor receptor 2 gene ca... | ACCEPT | Summary: PMID:7987400 demonstrates that mutations in FGFR2 cause Crouzon syndrome, providing additional genetic evidence for FGFR2 role in cranial skeleton development. Multiple mutations in the B exon (IIIc domain) were identified. Reason: Complements PMID:7874170 evidence. Crouzon syndrome is autosomal dominant craniosynostosis caused by FGFR2 mutations, including cysteine substitutions in the Ig-like domain. Core developmental function. Supporting Evidence: PMID:7987400 We now present evidence that mutations in the fibroblast growth factor receptor 2 gene (FGFR2) cause Crouzon syndrome. |
| GO:0005634 nucleus | IDA PMID:16597614 FGF-10 and its receptor exhibit bidirectional paracrine targ... | KEEP AS NON CORE | Summary: PMID:16597614 observed FGF-10 receptor (FGFR2IIIb/KGFR) in nucleus of urothelial cells by microscopy. This is an intriguing finding suggesting nuclear translocation of activated receptor, though unconventional. Reason: Nuclear localization of FGFRs has been reported but is non-canonical and represents a specialized signaling mechanism rather than the primary localization. The main function of FGFR2 is at the plasma membrane. Supporting Evidence: PMID:16597614 Deconvolution, light and transmission electron microscopic studies captured FGF-10 and its receptor in association with the urothelial cell surface, in cytoplasm, and within nuclei |
| GO:0005737 cytoplasm | IDA PMID:16597614 FGF-10 and its receptor exhibit bidirectional paracrine targ... | ACCEPT | Summary: PMID:16597614 showed FGFR2 (FGF-10 receptor) localizes to cytoplasm during its trafficking and signaling in urothelial cells. Reason: FGFR2 is found in cytoplasm during biosynthesis, trafficking to plasma membrane, and after receptor internalization. Valid localization. Supporting Evidence: PMID:16597614 Deconvolution, light and transmission electron microscopic studies captured FGF-10 and its receptor in association with the urothelial cell surface, in cytoplasm, and within nuclei |
| GO:0009986 cell surface | IDA PMID:16597614 FGF-10 and its receptor exhibit bidirectional paracrine targ... | ACCEPT | Summary: PMID:16597614 localized FGFR2 (FGF-10 receptor) to the urothelial cell surface, consistent with its function as a transmembrane receptor. Reason: Cell surface localization is expected for transmembrane receptor tyrosine kinases. This is functionally equivalent to plasma membrane localization. Supporting Evidence: PMID:16597614 Deconvolution, light and transmission electron microscopic studies captured FGF-10 and its receptor in association with the urothelial cell surface |
| GO:0005007 fibroblast growth factor receptor activity | IDA PMID:15629145 Tyrosine 769 of the keratinocyte growth factor receptor is r... | ACCEPT | Summary: PMID:15629145 studied KGFR (FGFR2IIIb) signaling through autophosphorylation and downstream pathway activation. The study demonstrated functional FGF receptor activity through tyrosine phosphorylation assays. Reason: Direct experimental demonstration of FGFR2 (KGFR isoform) receptor activity including autophosphorylation and signaling. Core molecular function. Supporting Evidence: PMID:15629145 KGFR is rapidly autophosphorylated on specific tyrosine residues in the intracellular domain, recruits substrate proteins |
| GO:0005007 fibroblast growth factor receptor activity | IDA PMID:8663044 Receptor specificity of the fibroblast growth factor family. | ACCEPT | Summary: PMID:8663044 systematically tested FGF receptor splice variants for ligand specificity and mitogenic activity. This landmark study established FGFR2 isoform-specific ligand binding and receptor activation. Reason: Comprehensive biochemical characterization of FGFR2 splice variants as functional FGF receptors. Demonstrated mitogenic activity with multiple FGF ligands. Foundational study for FGFR2 biology. Supporting Evidence: PMID:8663044 we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. |
| GO:0005886 plasma membrane | IDA PMID:15629145 Tyrosine 769 of the keratinocyte growth factor receptor is r... | ACCEPT | Summary: PMID:15629145 studied KGFR (FGFR2IIIb) at the plasma membrane where it undergoes ligand-induced internalization. Reason: Plasma membrane localization is the primary site of FGFR2 function as a transmembrane receptor. Supporting Evidence: PMID:15629145 Tyrosine 769 of the keratinocyte growth factor receptor is required for receptor signaling but not endocytosis. |
| GO:0005886 plasma membrane | IDA PMID:16844695 Intracellular retention, degradation, and signaling of glyco... | ACCEPT | Summary: PMID:16844695 studied FGFR2 trafficking and localization, showing wild-type FGFR2 localizes to plasma membrane while glycosylation-deficient and mutant forms show altered localization. Reason: Demonstrates plasma membrane is the normal localization for properly processed FGFR2, while mutations affecting glycosylation impair trafficking. Supporting Evidence: PMID:16844695 we show that trafficking and autoactivation of wild type FGFR2 is glycosylation-dependent |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:15629145 Tyrosine 769 of the keratinocyte growth factor receptor is r... | ACCEPT | Summary: PMID:15629145 showed that KGFR Y769F mutation impairs cell proliferation, demonstrating that functional KGFR (FGFR2IIIb) signaling promotes proliferation. Reason: Mutant phenotype analysis demonstrates FGFR2 promotes cell proliferation. Core biological process for FGFR signaling. Supporting Evidence: PMID:15629145 tyrosine 769 is required...for cell proliferation through the regulation of FRS2 tyrosine phosphorylation |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:8663044 Receptor specificity of the fibroblast growth factor family. | ACCEPT | Summary: PMID:8663044 used mitogenic assays to demonstrate FGF-induced proliferation through FGFR2. Multiple FGF ligands activated FGFR2-expressing cells. Reason: Direct mitogenic assays showing FGFR2 activation promotes cell proliferation. Foundational evidence for this core biological process. Supporting Evidence: PMID:8663044 Receptor specificity of the fibroblast growth factor family. |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IDA PMID:15629145 Tyrosine 769 of the keratinocyte growth factor receptor is r... | ACCEPT | Summary: PMID:15629145 characterized KGFR signaling pathway including PLCgamma recruitment, FRS2 phosphorylation, and MAPK activation. This directly demonstrates FGF receptor signaling. Reason: Detailed characterization of FGFR2 (KGFR) signaling pathway components. Core biological process. Supporting Evidence: PMID:15629145 tyrosine 769 is required for the binding to KGFR and tyrosine phosphorylation of PLCgamma as well as for the full activation of MAPKs |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IDA PMID:8663044 Receptor specificity of the fibroblast growth factor family. | ACCEPT | Summary: PMID:8663044 demonstrated FGF signaling through FGFR2 using mitogenic assays as readout of pathway activation. Reason: Functional demonstration of FGF signaling pathway activation through FGFR2. Supporting Evidence: PMID:8663044 Receptor specificity of the fibroblast growth factor family. |
| GO:0010518 positive regulation of phospholipase activity | IMP PMID:16844695 Intracellular retention, degradation, and signaling of glyco... | ACCEPT | Summary: PMID:16844695 showed both wild-type and mutant FGFR2 signal through PLCgamma. The C278F mutation and unglycosylated FGFR2 signal through PLCgamma in a ligand-independent manner. Reason: Demonstrates FGFR2 activates PLCgamma (phospholipase C gamma), which is a well-established downstream effector of FGFR signaling. Supporting Evidence: PMID:16844695 Both FGFR2C278F and unglycosylated wild type FGFR2 signal through phospholipase Cgamma in a ligand-independent manner |
| GO:0017134 fibroblast growth factor binding | IDA PMID:8663044 Receptor specificity of the fibroblast growth factor family. | ACCEPT | Summary: PMID:8663044 systematically characterized FGF binding specificity of FGFR2 splice variants. FGF1 binds all variants; FGF2 binds IIIc; FGF7 binds IIIb. Reason: Comprehensive biochemical characterization of FGF binding to FGFR2 isoforms. Core molecular function. Established isoform-specific ligand preferences. Supporting Evidence: PMID:8663044 FGF 1 is the only FGF that can activate all FGF receptor splice variants |
| GO:0018108 peptidyl-tyrosine phosphorylation | IDA PMID:15629145 Tyrosine 769 of the keratinocyte growth factor receptor is r... | ACCEPT | Summary: PMID:15629145 demonstrated KGFR (FGFR2IIIb) phosphorylates tyrosine residues on PLCgamma and FRS2 substrates. The study showed Y769 is required for PLCgamma and FRS2 tyrosine phosphorylation. Reason: Direct demonstration of FGFR2 tyrosine kinase activity phosphorylating substrates. Core enzymatic function of receptor tyrosine kinases. Supporting Evidence: PMID:15629145 tyrosine 769 is required for the binding to KGFR and tyrosine phosphorylation of PLCgamma...through the regulation of FRS2 tyrosine phosphorylation |
| GO:0018108 peptidyl-tyrosine phosphorylation | IDA PMID:16844695 Intracellular retention, degradation, and signaling of glyco... | ACCEPT | Summary: PMID:16844695 showed FGFR2 phosphorylates itself and downstream substrates. Both wild-type and mutant FGFR2 exhibit tyrosine phosphorylation activity. Reason: Confirms FGFR2 tyrosine kinase activity in phosphorylating substrates. Supporting Evidence: PMID:16844695 2006 Jul 14. Intracellular retention, degradation, and signaling of glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F. |
| GO:0033688 regulation of osteoblast proliferation | TAS PMID:15190072 Cbl-mediated degradation of Lyn and Fyn induced by constitut... | ACCEPT | Summary: PMID:15190072 studied FGFR2 S252W gain-of-function mutation in osteoblasts. The study shows constitutive FGFR2 activation affects osteoblast proliferation through regulation of Src family kinases Lyn and Fyn. Reason: Direct evidence that FGFR2 regulates osteoblast proliferation. This function is highly relevant to craniosynostosis syndromes caused by FGFR2 mutations. Supporting Evidence: PMID:15190072 Fibroblast growth factors (FGFs) play an important regulatory role in skeletal development and bone formation |
| GO:0042803 protein homodimerization activity | IPI PMID:16844695 Intracellular retention, degradation, and signaling of glyco... | ACCEPT | Summary: PMID:16844695 studied FGFR2 homodimerization which is required for receptor activation. FGFR2 dimerizes upon ligand binding or constitutively in gain-of-function mutants. Reason: FGFR2 homodimerization is essential for receptor activation. Documented by immunoprecipitation studies. Core mechanism of receptor activation. Supporting Evidence: PMID:16844695 2006 Jul 14. Intracellular retention, degradation, and signaling of glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F. |
| GO:0043410 positive regulation of MAPK cascade | IMP PMID:15629145 Tyrosine 769 of the keratinocyte growth factor receptor is r... | ACCEPT | Summary: PMID:15629145 showed that KGFR Y769F mutation impairs MAPK activation, demonstrating that functional FGFR2 signaling is required for full MAPK cascade activation. Reason: Mutant phenotype analysis confirms FGFR2 activates MAPK cascade. Core downstream signaling pathway. Supporting Evidence: PMID:15629145 tyrosine 769 is required...for the full activation of MAPKs |
| GO:0045667 regulation of osteoblast differentiation | TAS PMID:15190072 Cbl-mediated degradation of Lyn and Fyn induced by constitut... | ACCEPT | Summary: PMID:15190072 demonstrated that constitutive FGFR2 activation promotes osteoblast differentiation through Cbl-mediated degradation of Src family kinases Lyn and Fyn. Reason: Direct evidence that FGFR2 regulates osteoblast differentiation. The FGFR2 S252W mutation (Apert syndrome) increases ALP expression, a marker of osteoblast differentiation. Supporting Evidence: PMID:15190072 constitutive FGFR2 activation induces c-Cbl-dependent Lyn and Fyn proteasome degradation, resulting in...increased ALP expression |
| GO:0046777 protein autophosphorylation | IDA PMID:15629145 Tyrosine 769 of the keratinocyte growth factor receptor is r... | ACCEPT | Summary: PMID:15629145 demonstrated KGFR (FGFR2IIIb) autophosphorylation on tyrosine residues including Y769 upon ligand binding. Reason: Direct demonstration of FGFR2 autophosphorylation. Core mechanism of receptor tyrosine kinase activation. Supporting Evidence: PMID:15629145 KGFR is rapidly autophosphorylated on specific tyrosine residues in the intracellular domain |
| GO:0048705 skeletal system morphogenesis | TAS PMID:15190072 Cbl-mediated degradation of Lyn and Fyn induced by constitut... | ACCEPT | Summary: PMID:15190072 discusses FGFR2 role in skeletal development. FGFR2 mutations cause skeletal abnormalities including craniosynostosis. Reason: FGFR2 is essential for skeletal system development. Mutations cause multiple craniosynostosis syndromes affecting skull development. Supporting Evidence: PMID:15190072 Fibroblast growth factors (FGFs) play an important regulatory role in skeletal development and bone formation |
| GO:0035602 fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation transferred from mouse ortholog. Overly specific term for a context-dependent function that is not a primary role for human FGFR2. Reason: While FGF signaling can have anti-apoptotic effects, this highly specific term (bone marrow cell apoptosis) is not a core function of human FGFR2. Mouse knockout data may not directly translate to primary human function. |
| GO:0035603 fibroblast growth factor receptor signaling pathway involved in hemopoiesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation transferred from mouse ortholog. Hemopoiesis is not a primary function of FGFR2; this likely reflects pleiotropic effects in mouse models. Reason: FGFR2 primary functions are in epithelial-mesenchymal signaling, skeletal development, and wound healing. Hemopoietic role is not a core function. |
| GO:0035604 fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation transferred from mouse ortholog. Overly specific term for bone marrow context that is not a primary FGFR2 function. Reason: While FGFR2 promotes proliferation generally, this bone marrow-specific context is not a core function for human FGFR2. |
| GO:0035607 fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. FGFR2 has roles in brain development but this specific term for orbitofrontal cortex is highly specialized. Reason: Brain development role is plausible given FGFR2 mutations cause Crouzon and Apert syndromes which can have CNS effects. However, this is a very specific developmental context, not a core function. |
| GO:0021769 orbitofrontal cortex development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for orbitofrontal cortex development. Related to the above signaling pathway annotation. Reason: Specialized developmental context. FGFR2 contributes to brain development but this specific region is not a core function. |
| GO:0021847 ventricular zone neuroblast division | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for neural progenitor division in the ventricular zone during brain development. Reason: FGF signaling has roles in neural development but this is a specialized developmental function, not a core FGFR2 function. |
| GO:0021860 pyramidal neuron development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for pyramidal neuron development. Reason: Specialized neuronal development context. Not a primary FGFR2 function. |
| GO:0045787 positive regulation of cell cycle | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 promotes cell proliferation which involves positive regulation of the cell cycle. Reason: Consistent with FGFR2 role in promoting cell proliferation. Mitogenic signaling through FRS2/MAPK pathway drives cell cycle progression. |
| GO:0060076 excitatory synapse | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation from mouse ortholog suggesting FGFR2 localization at excitatory synapses. Unusual localization for a growth factor receptor. Reason: Synaptic localization is not a core function of FGFR2. May reflect specialized neuronal signaling in mouse models but not a primary human FGFR2 function. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. Indirect effect of FGFR2 signaling on transcription through downstream pathways. Reason: FGFR2 signaling can affect transcription through MAPK and other pathways, but transcriptional regulation is an indirect downstream effect, not a core molecular function of the receptor. |
| GO:0001525 angiogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. Duplicate of IBA annotation - FGF signaling has documented roles in angiogenesis. Reason: Consistent with IBA annotation. Angiogenesis is a documented but non-core function for FGFR2; FGFR1 may be more prominent in vascular biology. |
| GO:0001657 ureteric bud development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. FGFR2 has roles in kidney development including ureteric bud branching morphogenesis. Reason: UniProt notes FGFR2 is required for normal embryonic patterning including organogenesis. Kidney development is a documented but tissue-specific developmental function. |
| GO:0001701 in utero embryonic development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. FGFR2 is required for normal embryonic development as evidenced by embryonic lethality in knockout mice. Reason: Very broad developmental term. FGFR2 is essential for development but more specific terms (limb, lung, skeletal) better capture core functions. |
| GO:0002053 positive regulation of mesenchymal cell proliferation | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2IIIc (mesenchymal isoform) promotes mesenchymal cell proliferation in response to FGF2/4 from epithelium. Reason: Core function for FGFR2IIIc isoform. Mesenchymal proliferation is central to epithelial-mesenchymal signaling that FGFR2 mediates in development. |
| GO:0003148 outflow tract septum morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. Cardiac outflow tract development involves FGFR signaling but is a specialized developmental context. Reason: Cardiac development role is documented for FGFRs but this specific structure is not a core FGFR2 function. |
| GO:0003149 membranous septum morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. Cardiac septum development is a specialized developmental context. Reason: Specialized cardiac developmental function, not a core FGFR2 function. |
| GO:0007267 cell-cell signaling | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 mediates paracrine signaling between epithelium and mesenchyme. Reason: Core function. FGFR2 mediates paracrine FGF signaling between cell types, particularly epithelial-mesenchymal communication where IIIb receives signals from mesenchyme and IIIc receives signals from epithelium. |
| GO:0007409 axonogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. FGF signaling has roles in axon guidance and neuronal development. Reason: Neural development role is documented but not a primary FGFR2 function. More specialized than core epithelial-mesenchymal signaling roles. |
| GO:0008589 regulation of smoothened signaling pathway | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation from mouse ortholog. Cross-talk between FGF and Hedgehog (Smoothened) pathways has been reported in development. Reason: While pathway cross-talk exists, direct regulation of Smoothened signaling is not a core FGFR2 function. This represents indirect developmental pathway interactions rather than a primary function. |
| GO:0009791 post-embryonic development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. FGFR2 has roles in tissue homeostasis and repair after embryonic development. Reason: FGFR2 continues to function in adult tissue homeostasis and wound healing but this is a broad term. Embryonic roles are better documented. |
| GO:0009880 embryonic pattern specification | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 contributes to embryonic patterning through epithelial-mesenchymal interactions. Reason: UniProt confirms FGFR2 is required for normal embryonic patterning. FGF signaling through FGFR2 establishes tissue boundaries and patterns during development. |
| GO:0009887 animal organ morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 is required for morphogenesis of multiple organs including limbs, lungs, and skeleton. Reason: Core developmental function. FGFR2 is essential for branching morphogenesis and organ development, particularly lungs, limbs, and craniofacial skeleton. |
| GO:0016331 morphogenesis of embryonic epithelium | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2IIIb is expressed in epithelium and receives signals from mesenchyme to direct epithelial morphogenesis. Reason: Core function for FGFR2IIIb isoform. Epithelial morphogenesis through FGF7/10 signaling is a primary developmental role. |
| GO:0022612 gland morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 is required for salivary gland, lacrimal gland, and other gland development through branching morphogenesis. Reason: Core developmental function. FGFR2-mediated branching morphogenesis is essential for gland development in multiple organ systems. |
| GO:0030177 positive regulation of Wnt signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. Cross-talk between FGF and Wnt pathways occurs during development but this is indirect signaling. Reason: FGF-Wnt pathway interactions exist during development but positive regulation of Wnt signaling is not a direct core function of FGFR2. |
| GO:0030282 bone mineralization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. FGFR2 regulates osteoblast differentiation and bone development; mineralization is a downstream effect. Reason: Indirect effect of FGFR2 on osteoblast function. The core function is regulating osteoblast proliferation/differentiation rather than mineralization per se. |
| GO:0030324 lung development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 is essential for lung branching morphogenesis. UniProt confirms role in lung morphogenesis. Reason: Core developmental function. FGFR2 (particularly IIIb/KGFR) is essential for lung epithelial branching morphogenesis through FGF10 signaling. |
| GO:0030855 epithelial cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2IIIb in epithelial cells regulates their differentiation in response to mesenchymal FGF signals. Reason: Core function for FGFR2IIIb isoform. Epithelial differentiation is directed by FGF7/10 signaling through the epithelial FGFR2 isoform. |
| GO:0030901 midbrain development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for midbrain development. Reason: Brain development is one of many developmental contexts where FGFR2 functions, but not a primary function. |
| GO:0030916 otic vesicle formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for inner ear development. Reason: Specialized developmental context. FGFR2 contributes to ear development but this is not a core function. |
| GO:0031069 hair follicle morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 is required for skin development including hair follicles. UniProt notes role in skin development. Reason: Documented role in skin development. FGF signaling through FGFR2IIIb contributes to epithelial appendage formation including hair follicles. |
| GO:0032808 lacrimal gland development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. Lacrimal gland develops through branching morphogenesis requiring FGFR2 signaling. Reason: Example of gland morphogenesis role. More general gland morphogenesis term already captures this function. |
| GO:0035265 organ growth | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 promotes cell proliferation which contributes to organ growth during development. Reason: General term consistent with FGFR2 role in promoting proliferation during organ development. |
| GO:0042472 inner ear morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for inner ear development. Reason: Specialized developmental context for ear morphogenesis. |
| GO:0042476 odontogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. FGF signaling is involved in tooth development through epithelial-mesenchymal interactions. Reason: Tooth development involves FGFR2 but is a specialized developmental context rather than a core function. |
| GO:0045165 cell fate commitment | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. FGFR2 signaling influences cell fate decisions during development. Reason: Broad developmental term. FGFR2 influences cell fate but more specific terms better capture its functions. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. FGFR2 signaling can activate transcription through MAPK pathway and transcription factors. Reason: Indirect downstream effect of FGFR2 signaling rather than a core molecular function of the receptor. |
| GO:0048286 lung alveolus development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. Specific aspect of lung development where FGFR2 contributes to alveolar formation. Reason: Part of core lung development function. FGFR2 is essential for lung morphogenesis including alveolar development. |
| GO:0048557 embryonic digestive tract morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for GI tract development. Reason: One of many organs where FGFR2 contributes to development but not a primary documented function. |
| GO:0048562 embryonic organ morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. General term for FGFR2 role in organ development during embryogenesis. Reason: Core developmental function. FGFR2 is essential for morphogenesis of multiple organs through epithelial-mesenchymal interactions. |
| GO:0048565 digestive tract development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for GI tract development. Reason: Digestive tract development is one of many developmental contexts. |
| GO:0048568 embryonic organ development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. Broad term for embryonic organogenesis role of FGFR2. Reason: Core developmental function consistent with FGFR2 role in multiple organ systems during development. |
| GO:0048608 reproductive structure development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for reproductive organ development. Reason: Specialized developmental context not emphasized in human FGFR2 function. |
| GO:0048730 epidermis morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 is required for skin development. UniProt confirms role in skin development. Reason: Documented function. FGFR2IIIb in keratinocytes responds to FGF7/KGF from dermal fibroblasts to regulate epidermis. |
| GO:0048755 branching morphogenesis of a nerve | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for nerve branching. Reason: Specialized neural context not a primary FGFR2 function. |
| GO:0048762 mesenchymal cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2IIIc in mesenchyme responds to epithelial FGFs to promote mesenchymal differentiation. Reason: Core function for FGFR2IIIc isoform. Mesenchymal differentiation is central to FGFR2 role in development. |
| GO:0050679 positive regulation of epithelial cell proliferation | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2IIIb promotes epithelial cell proliferation in response to FGF7/10. UniProt confirms proliferation in keratinocytes. Reason: Core function for FGFR2IIIb isoform. Epithelial proliferation is a primary response to FGF7/10 signaling. |
| GO:0051150 regulation of smooth muscle cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for smooth muscle differentiation. Reason: Specialized context for FGFR2 function in mesenchymal differentiation. |
| GO:0051781 positive regulation of cell division | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 promotes cell proliferation which involves cell division. Reason: Consistent with core mitogenic function of FGFR2 signaling. |
| GO:0055010 ventricular cardiac muscle tissue morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for cardiac development. Reason: Cardiac development context is not a primary FGFR2 function. |
| GO:0060045 positive regulation of cardiac muscle cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for cardiac muscle proliferation. Reason: Specialized cardiac context not a primary FGFR2 function. |
| GO:0060174 limb bud formation | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 is essential for limb bud development. UniProt confirms role in limb bud development. Reason: Core developmental function. FGFR2 is required for limb bud outgrowth and patterning through FGF signaling. |
| GO:0060348 bone development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 is essential for bone development; mutations cause craniosynostosis syndromes. Reason: Core developmental function. FGFR2 mutations in humans cause multiple skeletal syndromes demonstrating essential role in osteogenesis. |
| GO:0060349 bone morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 regulates bone shape through effects on osteoblast function. Reason: Core function evidenced by craniosynostosis syndromes where FGFR2 mutations cause abnormal skull bone morphology. |
| GO:0060442 branching involved in prostate gland morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. Prostate gland develops through branching morphogenesis involving FGFR2. Reason: Specific example of branching morphogenesis. General gland morphogenesis term captures this function. |
| GO:0060445 branching involved in salivary gland morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. Salivary gland develops through FGFR2-dependent branching morphogenesis. Reason: Well-documented example of FGFR2-dependent branching morphogenesis. FGF10/FGFR2IIIb signaling is essential for salivary gland development. |
| GO:0060449 bud elongation involved in lung branching | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. Specific aspect of lung branching morphogenesis involving bud outgrowth. Reason: Core lung development function. FGF10/FGFR2IIIb signaling drives epithelial bud elongation in lung branching. |
| GO:0060463 lung lobe morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog for lung lobe formation. Reason: Part of core lung development function of FGFR2. |
| GO:0060484 lung-associated mesenchyme development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2IIIc in lung mesenchyme responds to epithelial FGFs during development. Reason: Core lung development function. Both epithelial (IIIb) and mesenchymal (IIIc) FGFR2 isoforms contribute to lung development. |
| GO:0060501 positive regulation of epithelial cell proliferation involved in lung morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGF10/FGFR2IIIb signaling promotes lung epithelial proliferation during branching morphogenesis. Reason: Core function for lung development. FGFR2IIIb-mediated epithelial proliferation is essential for lung morphogenesis. |
| GO:0060512 prostate gland morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for prostate development. Reason: Specific gland development context. More general gland morphogenesis captures this function. |
| GO:0060523 prostate epithelial cord elongation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for prostate development. Reason: Specific prostate developmental context. More general epithelial morphogenesis and gland development terms capture this function. |
| GO:0060527 prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for highly specific prostate morphogenesis. Reason: Overly specific developmental term. General gland morphogenesis captures FGFR2 role without this level of specificity. |
| GO:0060529 squamous basal epithelial stem cell differentiation involved in prostate gland acinus development | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation from mouse ortholog for very specific prostate stem cell context. Reason: Extremely specific term that goes beyond core FGFR2 function. This level of specificity is not a primary FGFR2 function. |
| GO:0060601 lateral sprouting from an epithelium | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. Epithelial sprouting is part of branching morphogenesis that FGFR2 mediates. Reason: Consistent with FGFR2 role in branching morphogenesis. Lateral sprouting is a core mechanism of epithelial branching in lungs and glands. |
| GO:0060615 mammary gland bud formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. Mammary gland develops through FGFR2-dependent mechanisms similar to other glands. Reason: Example of gland morphogenesis. General gland development terms capture this function. |
| GO:0060664 epithelial cell proliferation involved in salivary gland morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGF10/FGFR2IIIb signaling promotes epithelial proliferation in salivary gland development. Reason: Core function for salivary gland development which is a well-documented FGFR2 function through epithelial-mesenchymal interactions. |
| GO:0060667 branch elongation involved in salivary gland morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. Branch elongation is a key aspect of salivary gland branching morphogenesis. Reason: Core salivary gland development function. Consistent with FGFR2 role in branching morphogenesis. |
| GO:0060670 branching involved in labyrinthine layer morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog for placental labyrinthine layer. Reason: Placental development context. UniProt notes trophoblast function but this specific aspect is not emphasized. |
| GO:0060688 regulation of morphogenesis of a branching structure | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 is a key regulator of branching morphogenesis in multiple organs. Reason: Core developmental function. FGFR2 regulates branching morphogenesis in lungs, glands, and other organs through epithelial-mesenchymal signaling. |
| GO:0060915 mesenchymal cell differentiation involved in lung development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2IIIc in lung mesenchyme responds to epithelial signals to regulate mesenchymal differentiation. Reason: Core lung development function. Both epithelial (IIIb) and mesenchymal (IIIc) FGFR2 isoforms contribute to lung development. |
| GO:0060916 mesenchymal cell proliferation involved in lung development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2IIIc in lung mesenchyme promotes proliferation in response to epithelial FGFs. Reason: Core lung development function for FGFR2IIIc isoform. |
| GO:0070372 regulation of ERK1 and ERK2 cascade | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 activates ERK1/2 (MAPK3/MAPK1) through the RAS-MAPK pathway. Reason: Core signaling function. ERK1/2 cascade activation is a primary downstream effect of FGFR2 signaling through FRS2/GRB2/SOS/RAS pathway. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from mouse ortholog. FGFR2 positively regulates ERK1/2 cascade activation. Reason: Core signaling function. More specific child term of MAPK cascade regulation that is well-documented for FGFR2. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from mouse ortholog. Cross-talk between FGF and Wnt pathways occurs during development. Reason: Indirect pathway cross-talk rather than a direct core function of FGFR2. More specific than general Wnt regulation annotation already reviewed. |
| GO:0016020 membrane | NAS PMID:8676562 [Nucleotide sequences at intron 6 and exon 7 junction of fib... | ACCEPT | Summary: NAS annotation for membrane localization. FGFR2 is a transmembrane receptor. Reason: Correct but general term. More specific plasma membrane annotations exist. Supporting Evidence: PMID:8676562 Apert syndrome, acrocephalosyndactyly Type I, is an autosomal dominant craniosynostosis comprising acrocephaly, facial dysmorphism and severe syndactyly of the hands and feet. |
| GO:0005634 nucleus | IDA PMID:17471512 Translocation of fibroblast growth factor-10 and its recepto... | KEEP AS NON CORE | Summary: PMID:17471512 demonstrated nuclear localization of FGF-10 receptor (FGFR2IIIb) in urothelial cells along with its ligand FGF-10. Reason: Nuclear localization represents a specialized signaling mechanism rather than the primary localization. Main FGFR2 function is at plasma membrane. Supporting Evidence: PMID:17471512 The FGF-10 receptor was observed in cell nuclei regardless of the presence or concentration of exogenous rFGF-10 ligand |
| GO:0005737 cytoplasm | IDA PMID:17471512 Translocation of fibroblast growth factor-10 and its recepto... | ACCEPT | Summary: PMID:17471512 showed FGF-10 receptor (FGFR2IIIb) localizes to cytoplasm in urothelial cells during trafficking. Reason: FGFR2 is found in cytoplasm during biosynthesis, trafficking, and after internalization. Supporting Evidence: PMID:17471512 rFGF-10(no NLS) was found in cytoplasm to a far greater degree than rFGF-10 |
| GO:0005938 cell cortex | IDA PMID:17471512 Translocation of fibroblast growth factor-10 and its recepto... | KEEP AS NON CORE | Summary: PMID:17471512 may have observed FGFR2 at the cell cortex during trafficking or at the plasma membrane interface. Reason: Cell cortex localization is not a primary FGFR2 localization. May represent trafficking intermediate or plasma membrane-associated pool. Supporting Evidence: PMID:17471512 Translocation of fibroblast growth factor-10 and its receptor into nuclei of human urothelial cells. |
| GO:0008284 positive regulation of cell population proliferation | IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family. | ACCEPT | Summary: IGI (Inferred from Genetic Interaction) annotation from PMID:8663044 which tested multiple FGF-FGFR combinations for mitogenic activity. Reason: Consistent with core mitogenic function. PMID:8663044 demonstrated proliferative activity of FGFR2 with various FGF ligands. Supporting Evidence: PMID:8663044 Receptor specificity of the fibroblast growth factor family. |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family. | ACCEPT | Summary: IGI annotation from PMID:8663044 demonstrating FGF receptor signaling through FGFR2. Reason: Core biological process. PMID:8663044 is foundational study for FGFR signaling specificity. Supporting Evidence: PMID:8663044 Receptor specificity of the fibroblast growth factor family. |
| GO:0005007 fibroblast growth factor receptor activity | IGI PMID:10830168 Crystal structures of two FGF-FGFR complexes reveal the dete... | ACCEPT | Summary: IGI annotation from PMID:10830168 which determined crystal structures of FGF-FGFR complexes and characterized ligand-receptor specificity. Reason: Core molecular function. PMID:10830168 provided structural basis for FGF receptor specificity through alternative splicing. Supporting Evidence: PMID:10830168 Specificity is achieved through interactions between the N-terminal and central regions of FGFs and two loop regions in D3 that are subject to alternative splicing |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IPI PMID:10830168 Crystal structures of two FGF-FGFR complexes reveal the dete... | ACCEPT | Summary: IPI annotation from PMID:10830168 based on physical interaction studies of FGF-FGFR complexes. Reason: Core signaling pathway. Crystal structures revealed basis for ligand binding and receptor activation. Supporting Evidence: PMID:10830168 Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. |
| GO:0017134 fibroblast growth factor binding | IPI PMID:8386828 Activation of fibroblast growth factor (FGF) receptors by re... | ACCEPT | Summary: IPI annotation from PMID:8386828 demonstrating FGF-5 binding to FGFR2. Competition binding studies showed KD of 0.5-1.5 nM. Reason: Core molecular function. Direct binding assays demonstrated FGF binding to FGFR2 with high affinity. Supporting Evidence: PMID:8386828 the KD for FGF-5-FGFR-1 and FGF-5-FGFR-2 interactions are both between 0.5 and 1.5 x 10(-9) M |
| GO:0005007 fibroblast growth factor receptor activity | NAS PMID:8676562 [Nucleotide sequences at intron 6 and exon 7 junction of fib... | ACCEPT | Summary: NAS annotation for FGF receptor activity. Duplicate annotation with different evidence code. Reason: Core molecular function supported by multiple evidence types. Supporting Evidence: PMID:8676562 Apert syndrome, acrocephalosyndactyly Type I, is an autosomal dominant craniosynostosis comprising acrocephaly, facial dysmorphism and severe syndactyly of the hands and feet. |
| GO:0004713 protein tyrosine kinase activity | NAS PMID:1697263 Cloning and expression of two distinct high-affinity recepto... | ACCEPT | Summary: NAS annotation for protein tyrosine kinase activity. FGFR2 is a receptor tyrosine kinase. Reason: Core molecular function. FGFR2 is a well-characterized receptor tyrosine kinase (EC 2.7.10.1). Supporting Evidence: PMID:1697263 Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. |
| GO:0005007 fibroblast growth factor receptor activity | NAS PMID:1400433 A novel form of fibroblast growth factor receptor 2. Alterna... | ACCEPT | Summary: NAS annotation from PMID:1400433 which identified alternative splicing creating isoforms with different ligand specificities. Reason: Core molecular function. PMID:1400433 was important for understanding isoform-specific FGF binding. Supporting Evidence: PMID:1400433 A novel form of fibroblast growth factor receptor 2. |
| GO:0005007 fibroblast growth factor receptor activity | NAS PMID:1697263 Cloning and expression of two distinct high-affinity recepto... | ACCEPT | Summary: NAS annotation for FGF receptor activity. Duplicate with different reference. Reason: Core molecular function. Supporting Evidence: PMID:1697263 Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. |
| GO:0016020 membrane | NAS PMID:1697263 Cloning and expression of two distinct high-affinity recepto... | ACCEPT | Summary: NAS annotation for membrane localization. FGFR2 is a single-pass type I membrane protein. Reason: Correct but general term. More specific plasma membrane annotations exist. Supporting Evidence: PMID:1697263 Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. |
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