id: P21802
gene_symbol: FGFR2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
  - name: 1 (BEK, FGFR2IIIc)
    id: P21802-1
  - name: 2 (Short)
    id: P21802-2
    sequence_note: VSP_002978
  - name: 3 (BFR-1, FGFR2IIIb, KGFR)
    id: P21802-3
    sequence_note: VSP_002969, VSP_002970, VSP_002971,
  - name: 4 (K-sam)
    id: P21802-4
    sequence_note: VSP_002964, VSP_002969, VSP_002970,
  - name: 5 (K-sam-I, BEK, IgIIIc)
    id: P21802-5
    sequence_note: VSP_002975
  - name: 6 (K-sam-IIC2)
    id: P21802-6
    sequence_note: VSP_002975, VSP_002984
  - name: 7 (K-sam-IIC3)
    id: P21802-8
    sequence_note: VSP_002975, VSP_002978
  - name: 8 (K-sam-IV, Soluble KGFR)
    id: P21802-14
    sequence_note: VSP_002965, VSP_002966
  - name: 9 (K-sam-III)
    id: P21802-15
    sequence_note: VSP_002968
  - name: 10 (TK14)
    id: P21802-16
    sequence_note: VSP_002967, VSP_002975
  - name: '11'
    id: P21802-17
    sequence_note: VSP_002969, VSP_002970, VSP_002971,
  - name: 12 (K-sam-IIC1, KGFR, IgIIIb)
    id: P21802-18
    sequence_note: VSP_002969, VSP_002970, VSP_002971,
  - name: 13 (Soluble KGFR)
    id: P21802-19
    sequence_note: VSP_002969, VSP_002970, VSP_002971,
  - name: '14'
    id: P21802-20
    sequence_note: VSP_019608, VSP_019609
  - name: '15'
    id: P21802-21
    sequence_note: VSP_002964, VSP_041915
  - name: '16'
    id: P21802-22
    sequence_note: VSP_002964, VSP_002969, VSP_002970,
  - name: '17'
    id: P21802-23
    sequence_note: VSP_041914
existing_annotations:
  - term:
      id: GO:0005007
      label: fibroblast growth factor receptor activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "Tyrosine-protein kinase that acts as a cell-surface receptor
            for fibroblast growth factors"
        - reference_id: file:human/FGFR2/FGFR2-deep-research-falcon.md
          supporting_text: "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."
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "SUBCELLULAR LOCATION: Cell membrane; Single-pass type
            I membrane protein"
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "Promotes cell proliferation in keratinocytes and immature
            osteoblasts"
  - term:
      id: GO:0008543
      label: fibroblast growth factor receptor signaling pathway
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "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"
  - term:
      id: GO:0001525
      label: angiogenesis
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0043410
      label: positive regulation of MAPK cascade
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and
            the MAP kinase signaling pathway"
  - term:
      id: GO:0043235
      label: receptor complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        FGFR2 forms homodimers upon ligand binding and also forms complexes with
        heparan sulfate proteoglycan co-receptors. UniProt confirms "Homodimer after
        ligand binding."
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "Monomer. Homodimer after ligand binding."
  - term:
      id: GO:0017134
      label: fibroblast growth factor binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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).
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "Isoform 1 has high affinity for FGF1 and FGF2, but low
            affinity for FGF7. Isoform 3 has high affinity for FGF1 and FGF7"
  - term:
      id: GO:0000166
      label: nucleotide binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: ACCEPT
      reason: >-
        True but general. FGFR2 has a kinase domain that binds ATP. The more specific
        term "ATP binding" is also annotated and preferred.
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: >-
        FGFR2 is a protein kinase. The annotation is correct but "protein tyrosine
        kinase activity" is more specific and preferred.
      action: ACCEPT
      reason: >-
        Correct parent term. FGFR2 has documented kinase activity (EC 2.7.10.1).
        More specific child term annotations also exist.
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        FGFR2 is a receptor tyrosine kinase that autophosphorylates and phosphorylates
        substrates including PLCG1, FRS2, and PAK4 on tyrosine residues.
      action: ACCEPT
      reason: >-
        Core molecular function. UniProt confirms EC 2.7.10.1 classification and
        documents phosphorylation of multiple substrates. Applies to all kinase-
        containing isoforms.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "Phosphorylates PLCG1, FRS2 and PAK4"
  - term:
      id: GO:0004714
      label: transmembrane receptor protein tyrosine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000003
    review:
      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.
      action: ACCEPT
      reason: >-
        Most specific appropriate MF term for transmembrane FGFR2 isoforms. Note
        that secreted isoforms (P21802-14, P21802-19) lack transmembrane domain
        and kinase activity.
  - term:
      id: GO:0005007
      label: fibroblast growth factor receptor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        Duplicate of IBA annotation. FGFR2 is unambiguously an FGF receptor.
      action: ACCEPT
      reason: >-
        Core function - duplicates IBA annotation with different evidence. Correct.
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        FGFR2 kinase domain binds ATP. Crystal structures confirm ATP binding
        (PDB entries with ATP analogs).
      action: ACCEPT
      reason: >-
        Core function for kinase activity. Structural data confirms ATP binding site.
  - term:
      id: GO:0005576
      label: extracellular region
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      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.
      action: ACCEPT
      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.
  - term:
      id: GO:0005794
      label: Golgi apparatus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      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."
      action: ACCEPT
      reason: >-
        FGFR2 passes through Golgi during maturation. Also documented as
        "Golgi apparatus" in subcellular location. Represents trafficking intermediate.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "SUBCELLULAR LOCATION: Cell membrane; Single-pass type
            I membrane protein. Golgi apparatus."
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        Duplicate of IBA annotation. Plasma membrane localization for transmembrane
        isoforms is well established.
      action: ACCEPT
      reason: >-
        Correct - duplicates IBA with different evidence.
  - term:
      id: GO:0006915
      label: apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "Promotes cell proliferation in keratinocytes and immature
            osteoblasts, but promotes apoptosis in differentiated osteoblasts"
  - term:
      id: GO:0008201
      label: heparin binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        FGFR2 binds heparan sulfate glycosaminoglycans which serve as coreceptors.
        Heparin (a highly sulfated heparan sulfate) is used experimentally.
      action: ACCEPT
      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).
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "Affinity for fibroblast growth factors (FGFs) is increased
            by heparan sulfate glycosaminoglycans that function as coreceptors"
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        Duplicate of IBA annotation. FGFR2 promotes cell proliferation.
      action: ACCEPT
      reason: >-
        Correct - duplicates IBA with different evidence.
  - term:
      id: GO:0008543
      label: fibroblast growth factor receptor signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        Duplicate of IBA annotation. FGFR2 is a core component of FGF signaling.
      action: ACCEPT
      reason: >-
        Correct - duplicates IBA with different evidence.
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: >-
        Transmembrane FGFR2 isoforms are integral membrane proteins. This is a
        parent term of plasma membrane - overly general but not wrong.
      action: ACCEPT
      reason: >-
        Correct but general. More specific annotations (plasma membrane) exist.
  - term:
      id: GO:0016301
      label: kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        FGFR2 has kinase activity. This is a parent of the more specific protein
        tyrosine kinase activity annotations.
      action: ACCEPT
      reason: >-
        Correct but overly general. More specific annotations exist.
  - term:
      id: GO:0016740
      label: transferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Kinases are transferases (transfer phosphate groups). This is very general
        but technically correct.
      action: ACCEPT
      reason: >-
        Correct parent term. Very general but valid.
  - term:
      id: GO:0031410
      label: cytoplasmic vesicle
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      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."
      action: ACCEPT
      reason: >-
        Valid location during receptor trafficking/internalization.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "After ligand binding, the activated receptor is rapidly
            internalized and degraded"
  - term:
      id: GO:0033688
      label: regulation of osteoblast proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        FGFR2 regulates osteoblast proliferation - it promotes proliferation in
        immature osteoblasts. This is relevant to craniosynostosis syndromes caused
        by FGFR2 mutations.
      action: ACCEPT
      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."
  - term:
      id: GO:0043009
      label: chordate embryonic development
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      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."
      action: KEEP_AS_NON_CORE
      reason: >-
        Valid but very general developmental term. More specific developmental
        processes (limb, lung, skeleton) are better descriptors of FGFR2 function.
  - term:
      id: GO:0043410
      label: positive regulation of MAPK cascade
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        Duplicate annotation (IBA already reviewed). MAPK cascade activation is a
        core downstream signaling output of FGFR2.
      action: ACCEPT
      reason: >-
        Duplicates IBA with different evidence. Core signaling function.
  - term:
      id: GO:0045595
      label: regulation of cell differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        FGFR2 regulates differentiation of multiple cell types including osteoblasts,
        keratinocytes, and epithelial cells. This is a core function.
      action: ACCEPT
      reason: >-
        UniProt confirms role in "regulation of cell proliferation, differentiation,
        migration and apoptosis." Applies to both IIIb (epithelial differentiation)
        and IIIc (mesenchymal differentiation) isoforms.
  - term:
      id: GO:0048562
      label: embryonic organ morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      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."
      action: ACCEPT
      reason: >-
        Core developmental function. FGFR2 is essential for morphogenesis of
        multiple organs through epithelial-mesenchymal interactions. Consistent
        with ISS annotation for the same term.
      supported_by:
        - reference_id: UniProtKB:P21802
          supporting_text: "Required for normal embryonic patterning, trophoblast
            function, limb bud development, lung morphogenesis, osteogenesis and
            skin development"
  - term:
      id: GO:0048705
      label: skeletal system morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        FGFR2 is critical for skeletal development. Mutations cause multiple
        craniosynostosis syndromes (Crouzon, Apert, Pfeiffer, Jackson-Weiss).
      action: ACCEPT
      reason: >-
        UniProt confirms "required for normal skeleton development" and documents
        multiple skeletal disorder phenotypes from FGFR2 mutations.
  - term:
      id: GO:1904888
      label: cranial skeletal system development
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        FGFR2 is critical for cranial skeleton development. Mutations cause
        craniosynostosis - premature fusion of cranial sutures.
      action: ACCEPT
      reason: >-
        Strong evidence from human genetics - FGFR2 mutations cause Crouzon syndrome,
        Apert syndrome, Pfeiffer syndrome, and other craniosynostoses.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:10618369
    review:
      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.
      action: MODIFY
      reason: >-
        "Protein binding" is too generic for GO annotation. This paper documents
        FGF binding which is already captured by GO:0017134.
      proposed_replacement_terms:
        - id: GO:0017134
          label: fibroblast growth factor binding
      supported_by:
        - reference_id: PMID:10618369
          supporting_text: Structural interactions of fibroblast growth factor 
            receptor with its ligands.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:10830168
    review:
      summary: >-
        PMID:10830168 reports crystal structures of FGF-FGFR complexes. Shows
        determinants of ligand-receptor specificity. "Protein binding" is too generic.
      action: MODIFY
      reason: >-
        Paper specifically documents FGF binding. Should use GO:0017134 fibroblast
        growth factor binding instead.
      proposed_replacement_terms:
        - id: GO:0017134
          label: fibroblast growth factor binding
      supported_by:
        - reference_id: PMID:10830168
          supporting_text: Crystal structures of two FGF-FGFR complexes reveal 
            the determinants of ligand-receptor specificity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11390973
    review:
      summary: >-
        PMID:11390973 describes structural basis for FGFR2 activation in Apert
        syndrome, examining FGF2 binding. "Protein binding" is too generic.
      action: MODIFY
      reason: >-
        Paper documents FGF2 binding to FGFR2. Should use more specific term.
      proposed_replacement_terms:
        - id: GO:0017134
          label: fibroblast growth factor binding
      supported_by:
        - reference_id: PMID:11390973
          supporting_text: Structural basis for fibroblast growth factor 
            receptor 2 activation in Apert syndrome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:12591959
    review:
      summary: >-
        PMID:12591959 examines structural basis by which alternative splicing confers
        specificity in FGF receptors. Shows FGF10 binding to FGFR2IIIb.
      action: MODIFY
      reason: >-
        Paper documents isoform-specific FGF binding. Should use GO:0017134.
      proposed_replacement_terms:
        - id: GO:0017134
          label: fibroblast growth factor binding
      supported_by:
        - reference_id: PMID:12591959
          supporting_text: Structural basis by which alternative splicing 
            confers specificity in fibroblast growth factor receptors.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:1309608
    review:
      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.
      action: MODIFY
      reason: >-
        Classic paper on FGFR2 isoform-specific FGF binding. Should use GO:0017134.
      proposed_replacement_terms:
        - id: GO:0017134
          label: fibroblast growth factor binding
      supported_by:
        - reference_id: PMID:1309608
          supporting_text: 'Determination of ligand-binding specificity by alternative
            splicing: two distinct growth factor receptors encoded by a single gene.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22726438
    review:
      summary: >-
        PMID:22726438 documents inhibition of basal FGF receptor signaling by
        dimeric Grb2. Shows GRB2 interaction with FGFR2.
      action: MODIFY
      reason: >-
        Documents specific GRB2 binding. Should be annotated with a more specific
        term reflecting signaling adaptor interaction.
      proposed_replacement_terms:
        - id: GO:0005068
          label: transmembrane receptor protein tyrosine kinase adaptor activity
      supported_by:
        - reference_id: PMID:22726438
          supporting_text: Inhibition of basal FGF receptor signaling by dimeric
            Grb2.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23597563
    review:
      summary: >-
        PMID:23597563 describes molecular mechanism of SSR128129E, an extracellularly
        acting small-molecule allosteric inhibitor. Documents drug-receptor interaction.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        This paper is about drug binding, not protein-protein interaction. The
        "protein binding" annotation does not capture meaningful biology here.
      supported_by:
        - reference_id: PMID:23597563
          supporting_text: Molecular mechanism of SSR128129E, an extracellularly
            acting, small-molecule, allosteric inhibitor of FGF receptor 
            signaling.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25241761
    review:
      summary: >-
        PMID:25241761 uses in situ proximity ligation assay to profile endogenous
        protein-protein interactions. High-throughput interactome study.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        High-throughput study without specific functional characterization. "Protein
        binding" is too generic to be informative.
      supported_by:
        - reference_id: PMID:25241761
          supporting_text: Oct 9. Using an in situ proximity ligation assay to 
            systematically profile endogenous protein-protein interactions in a 
            pathway network.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26267536
    review:
      summary: >-
        PMID:26267536 describes long-pentraxin 3 derivative as FGF trap for cancer
        therapy. Documents FGF sequestration rather than receptor binding.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Paper focuses on therapeutic FGF trapping, not native FGFR2 interactions.
        "Protein binding" is not informative here.
      supported_by:
        - reference_id: PMID:26267536
          supporting_text: Long-Pentraxin 3 Derivative as a Small-Molecule FGF 
            Trap for Cancer Therapy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: >-
        PMID:33961781 is a large-scale proteome study of the human interactome.
        High-throughput data without specific functional characterization.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        High-throughput interactome study. "Protein binding" is too generic to be
        informative for specific gene annotation.
      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
            cell-specific remodeling of the human interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35384245
    review:
      summary: >-
        PMID:35384245 is a physical interactome atlas of human receptor tyrosine
        kinases. Large-scale study of RTK interactions.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        High-throughput interactome study. Generic "protein binding" annotations
        from such studies add little value.
      supported_by:
        - reference_id: PMID:35384245
          supporting_text: Physical and functional interactome atlas of human 
            receptor tyrosine kinases.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35922511
    review:
      summary: >-
        PMID:35922511 is a physical wiring diagram for the human immune system.
        Large-scale protein interaction study.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        High-throughput study. Generic "protein binding" from such studies is
        not informative for specific gene function.
      supported_by:
        - reference_id: PMID:35922511
          supporting_text: Aug 3. A physical wiring diagram for the human immune
            system.
  - term:
      id: GO:0001837
      label: epithelial to mesenchymal transition
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0003416
      label: endochondral bone growth
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        FGFR2 plays a role in bone development. Mutations cause craniosynostosis
        and affect skeletal growth.
      action: ACCEPT
      reason: >-
        Valid bone development function supported by disease phenotypes. UniProt
        documents FGFR2 role in osteogenesis and skeletal development.
  - term:
      id: GO:0009986
      label: cell surface
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        FGFR2 is a cell surface receptor. More specific than plasma membrane in
        indicating the exposed surface.
      action: ACCEPT
      reason: >-
        Valid localization. FGFR2 is a transmembrane receptor exposed at the cell
        surface for ligand binding.
  - term:
      id: GO:0017134
      label: fibroblast growth factor binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        Duplicate of IBA annotation. FGF binding is a core FGFR2 function.
      action: ACCEPT
      reason: >-
        Core function - duplicates IBA with different evidence.
  - term:
      id: GO:0032496
      label: response to lipopolysaccharide
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        LPS response is not a characterized FGFR2 function. This annotation may
        reflect expression changes rather than direct function.
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:0044344
      label: cellular response to fibroblast growth factor stimulus
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        FGFR2 mediates cellular response to FGF. This is its core function as an
        FGF receptor.
      action: ACCEPT
      reason: >-
        Core function. FGFR2 is the receptor that mediates cellular response to
        multiple FGFs.
  - term:
      id: GO:0045471
      label: response to ethanol
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Ethanol response is not a characterized FGFR2 function. This annotation
        likely reflects expression changes rather than direct function.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        No evidence that FGFR2 has a direct role in ethanol response. Likely
        ortholog transfer from expression data.
  - term:
      id: GO:0048333
      label: mesodermal cell differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        FGFR2IIIc (mesenchymal isoform) is involved in mesenchymal/mesodermal cell
        biology. This annotation may be partially isoform-specific.
      action: ACCEPT
      reason: >-
        Valid for FGFR2IIIc isoform specifically. FGF signaling through IIIc supports
        mesenchymal cell differentiation.
  - term:
      id: GO:0050680
      label: negative regulation of epithelial cell proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        This annotation seems contradictory to FGFR2's known role in promoting
        keratinocyte (epithelial) proliferation. The annotation may be context-
        specific or erroneous.
      action: UNDECIDED
      reason: >-
        UniProt states FGFR2 "promotes cell proliferation in keratinocytes" which
        contradicts negative regulation. May apply to specific contexts but unclear.
  - term:
      id: GO:0071300
      label: cellular response to retinoic acid
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Retinoic acid response is not a characterized FGFR2 function. May reflect
        expression regulation rather than functional response.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        No clear evidence for direct FGFR2 role in retinoic acid response. Likely
        ortholog transfer from expression data.
  - term:
      id: GO:0071456
      label: cellular response to hypoxia
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        Hypoxia response is not a well-characterized FGFR2 function. May reflect
        expression changes in hypoxia.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        No clear evidence for direct FGFR2 role in hypoxia response. Likely ortholog
        transfer from expression data.
  - term:
      id: GO:0071560
      label: cellular response to transforming growth factor beta stimulus
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        TGF-beta response may involve FGFR2 in certain contexts, especially related
        to EMT where both pathways interact.
      action: KEEP_AS_NON_CORE
      reason: >-
        There is crosstalk between FGF and TGF-beta pathways in EMT and development,
        but this is not a primary FGFR2 function.
  - term:
      id: GO:1904707
      label: positive regulation of vascular associated smooth muscle cell 
        proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: >-
        FGF signaling can promote smooth muscle cell proliferation, potentially via
        FGFR2IIIc in mesenchymal cells.
      action: KEEP_AS_NON_CORE
      reason: >-
        Valid but not a primary FGFR2 function. FGF2 signaling through FGFR can
        promote VSMC proliferation but this is not unique to FGFR2.
  - term:
      id: GO:0009986
      label: cell surface
    evidence_type: IDA
    original_reference_id: PMID:17959718
    review:
      summary: >-
        PMID:17959718 examines heparanase cleavage of perlecan and FGF10 activity
        in submandibular gland branching morphogenesis. Shows FGFR2 at cell surface.
      action: ACCEPT
      reason: >-
        Direct experimental evidence for cell surface localization during
        FGF10-FGFR2 signaling in branching morphogenesis.
      supported_by:
        - reference_id: PMID:17959718
          supporting_text: Heparanase cleavage of perlecan heparan sulfate 
            modulates FGF10 activity during ex vivo submandibular gland 
            branching morphogenesis.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654748
    review:
      summary: >-
        Reactome pathway annotation. Multiple Reactome entries document FGFR2
        plasma membrane localization in various signaling contexts.
      action: ACCEPT
      reason: >-
        Plasma membrane localization is well established for transmembrane FGFR2
        isoforms. Reactome pathway data supports this.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5655233
    review:
      summary: >-
        Reactome pathway annotation for FGFR2 signaling. Duplicates other PM annotations.
      action: ACCEPT
      reason: >-
        Valid localization, consistent with other evidence.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5655241
    review:
      summary: >-
        Reactome pathway annotation. Part of FGFR2 signaling pathway documentation.
      action: ACCEPT
      reason: >-
        Valid localization, consistent with other evidence.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5655245
    review:
      summary: >-
        Reactome pathway annotation for FGFR2 at plasma membrane.
      action: ACCEPT
      reason: >-
        Valid localization, duplicates other evidence.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5655268
    review:
      summary: >-
        Reactome pathway annotation for FGFR2 signaling.
      action: ACCEPT
      reason: >-
        Valid localization, consistent with established biology.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5655301
    review:
      summary: >-
        Reactome pathway annotation for FGFR2 signaling.
      action: ACCEPT
      reason: >-
        Valid localization.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5655320
    review:
      summary: >-
        Reactome pathway annotation for FGFR2 signaling.
      action: ACCEPT
      reason: >-
        Valid localization.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5655323
    review:
      summary: >-
        Reactome pathway annotation for FGFR2 signaling.
      action: ACCEPT
      reason: >-
        Valid localization.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5655339
    review:
      summary: >-
        Reactome pathway annotation for FGFR2 signaling.
      action: ACCEPT
      reason: >-
        Valid localization.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5655343
    review:
      summary: >-
        Reactome pathway annotation for FGFR2 signaling.
      action: ACCEPT
      reason: >-
        Valid localization.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8853313
    review:
      summary: >-
        Reactome pathway annotation for FGFR2 fusions autophosphorylation. Documents
        aberrant signaling in cancer.
      action: ACCEPT
      reason: >-
        Valid localization for wild-type and fusion FGFR2.
  - term:
      id: GO:0010839
      label: negative regulation of keratinocyte proliferation
    evidence_type: IMP
    original_reference_id: PMID:21412257
    review:
      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.
      action: REMOVE
      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.
      supported_by:
        - reference_id: PMID:21412257
          supporting_text: Mar 17. MiR-125b, a microRNA downregulated in 
            psoriasis, modulates keratinocyte proliferation by targeting FGFR2.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8853319
    review:
      summary: >-
        Reactome pathway annotation for plasma membrane localization. FGFR2
        transmembrane isoforms are plasma membrane receptors. Multiple Reactome
        pathways include FGFR2 at the plasma membrane.
      action: ACCEPT
      reason: >-
        Correct localization for transmembrane FGFR2 isoforms. Duplicate entries
        from different Reactome pathways reflect FGFR2 participation in multiple
        signaling contexts at the plasma membrane.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2029989
    review:
      summary: >-
        Reactome pathway annotation duplicate. Plasma membrane localization is
        well established for transmembrane FGFR2 isoforms.
      action: ACCEPT
      reason: >-
        Duplicate of other plasma membrane annotations from different Reactome
        pathway contexts. Valid for transmembrane isoforms.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2029983
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2029984
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2033472
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2033474
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2033479
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2033486
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2033488
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2033490
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2077424
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-109699
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-190413
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2316434
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2400009
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654147
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654157
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654159
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654397
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654399
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654402
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654404
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654406
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654407
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654562
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654603
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654605
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654607
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654608
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654612
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654614
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654615
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654618
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654620
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654622
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654677
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654697
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654701
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5654729
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5672965
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-190258
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-190260
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-190408
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-NUL-8853328
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2029988
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2029992
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2067713
    review:
      summary: >-
        Reactome pathway annotation duplicate for plasma membrane localization.
      action: ACCEPT
      reason: >-
        Valid duplicate annotation from different Reactome pathway.
  - term:
      id: GO:0048701
      label: embryonic cranial skeleton morphogenesis
    evidence_type: IMP
    original_reference_id: PMID:7874170
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:7874170
          supporting_text: "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."
  - term:
      id: GO:0048701
      label: embryonic cranial skeleton morphogenesis
    evidence_type: IMP
    original_reference_id: PMID:7987400
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:7987400
          supporting_text: "We now present evidence that mutations in the fibroblast
            growth factor receptor 2 gene (FGFR2) cause Crouzon syndrome."
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:16597614
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:16597614
          supporting_text: "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"
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:16597614
    review:
      summary: >-
        PMID:16597614 showed FGFR2 (FGF-10 receptor) localizes to cytoplasm during
        its trafficking and signaling in urothelial cells.
      action: ACCEPT
      reason: >-
        FGFR2 is found in cytoplasm during biosynthesis, trafficking to plasma
        membrane, and after receptor internalization. Valid localization.
      supported_by:
        - reference_id: PMID:16597614
          supporting_text: "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"
  - term:
      id: GO:0009986
      label: cell surface
    evidence_type: IDA
    original_reference_id: PMID:16597614
    review:
      summary: >-
        PMID:16597614 localized FGFR2 (FGF-10 receptor) to the urothelial cell
        surface, consistent with its function as a transmembrane receptor.
      action: ACCEPT
      reason: >-
        Cell surface localization is expected for transmembrane receptor tyrosine
        kinases. This is functionally equivalent to plasma membrane localization.
      supported_by:
        - reference_id: PMID:16597614
          supporting_text: "Deconvolution, light and transmission electron microscopic
            studies captured FGF-10 and its receptor in association with the urothelial
            cell surface"
  - term:
      id: GO:0005007
      label: fibroblast growth factor receptor activity
    evidence_type: IDA
    original_reference_id: PMID:15629145
    review:
      summary: >-
        PMID:15629145 studied KGFR (FGFR2IIIb) signaling through autophosphorylation
        and downstream pathway activation. The study demonstrated functional FGF
        receptor activity through tyrosine phosphorylation assays.
      action: ACCEPT
      reason: >-
        Direct experimental demonstration of FGFR2 (KGFR isoform) receptor activity
        including autophosphorylation and signaling. Core molecular function.
      supported_by:
        - reference_id: PMID:15629145
          supporting_text: "KGFR is rapidly autophosphorylated on specific tyrosine
            residues in the intracellular domain, recruits substrate proteins"
  - term:
      id: GO:0005007
      label: fibroblast growth factor receptor activity
    evidence_type: IDA
    original_reference_id: PMID:8663044
    review:
      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.
      action: ACCEPT
      reason: >-
        Comprehensive biochemical characterization of FGFR2 splice variants as
        functional FGF receptors. Demonstrated mitogenic activity with multiple
        FGF ligands. Foundational study for FGFR2 biology.
      supported_by:
        - reference_id: PMID:8663044
          supporting_text: "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."
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:15629145
    review:
      summary: >-
        PMID:15629145 studied KGFR (FGFR2IIIb) at the plasma membrane where it
        undergoes ligand-induced internalization.
      action: ACCEPT
      reason: >-
        Plasma membrane localization is the primary site of FGFR2 function as a
        transmembrane receptor.
      supported_by:
        - reference_id: PMID:15629145
          supporting_text: Tyrosine 769 of the keratinocyte growth factor 
            receptor is required for receptor signaling but not endocytosis.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:16844695
    review:
      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.
      action: ACCEPT
      reason: >-
        Demonstrates plasma membrane is the normal localization for properly
        processed FGFR2, while mutations affecting glycosylation impair trafficking.
      supported_by:
        - reference_id: PMID:16844695
          supporting_text: "we show that trafficking and autoactivation of wild type
            FGFR2 is glycosylation-dependent"
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: IMP
    original_reference_id: PMID:15629145
    review:
      summary: >-
        PMID:15629145 showed that KGFR Y769F mutation impairs cell proliferation,
        demonstrating that functional KGFR (FGFR2IIIb) signaling promotes
        proliferation.
      action: ACCEPT
      reason: >-
        Mutant phenotype analysis demonstrates FGFR2 promotes cell proliferation.
        Core biological process for FGFR signaling.
      supported_by:
        - reference_id: PMID:15629145
          supporting_text: "tyrosine 769 is required...for cell proliferation through
            the regulation of FRS2 tyrosine phosphorylation"
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: IDA
    original_reference_id: PMID:8663044
    review:
      summary: >-
        PMID:8663044 used mitogenic assays to demonstrate FGF-induced proliferation
        through FGFR2. Multiple FGF ligands activated FGFR2-expressing cells.
      action: ACCEPT
      reason: >-
        Direct mitogenic assays showing FGFR2 activation promotes cell proliferation.
        Foundational evidence for this core biological process.
      supported_by:
        - reference_id: PMID:8663044
          supporting_text: Receptor specificity of the fibroblast growth factor 
            family.
  - term:
      id: GO:0008543
      label: fibroblast growth factor receptor signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:15629145
    review:
      summary: >-
        PMID:15629145 characterized KGFR signaling pathway including PLCgamma
        recruitment, FRS2 phosphorylation, and MAPK activation. This directly
        demonstrates FGF receptor signaling.
      action: ACCEPT
      reason: >-
        Detailed characterization of FGFR2 (KGFR) signaling pathway components.
        Core biological process.
      supported_by:
        - reference_id: PMID:15629145
          supporting_text: "tyrosine 769 is required for the binding to KGFR and tyrosine
            phosphorylation of PLCgamma as well as for the full activation of MAPKs"
  - term:
      id: GO:0008543
      label: fibroblast growth factor receptor signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:8663044
    review:
      summary: >-
        PMID:8663044 demonstrated FGF signaling through FGFR2 using mitogenic
        assays as readout of pathway activation.
      action: ACCEPT
      reason: >-
        Functional demonstration of FGF signaling pathway activation through FGFR2.
      supported_by:
        - reference_id: PMID:8663044
          supporting_text: Receptor specificity of the fibroblast growth factor 
            family.
  - term:
      id: GO:0010518
      label: positive regulation of phospholipase activity
    evidence_type: IMP
    original_reference_id: PMID:16844695
    review:
      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.
      action: ACCEPT
      reason: >-
        Demonstrates FGFR2 activates PLCgamma (phospholipase C gamma), which is a
        well-established downstream effector of FGFR signaling.
      supported_by:
        - reference_id: PMID:16844695
          supporting_text: "Both FGFR2C278F and unglycosylated wild type FGFR2 signal
            through phospholipase Cgamma in a ligand-independent manner"
  - term:
      id: GO:0017134
      label: fibroblast growth factor binding
    evidence_type: IDA
    original_reference_id: PMID:8663044
    review:
      summary: >-
        PMID:8663044 systematically characterized FGF binding specificity of FGFR2
        splice variants. FGF1 binds all variants; FGF2 binds IIIc; FGF7 binds IIIb.
      action: ACCEPT
      reason: >-
        Comprehensive biochemical characterization of FGF binding to FGFR2 isoforms.
        Core molecular function. Established isoform-specific ligand preferences.
      supported_by:
        - reference_id: PMID:8663044
          supporting_text: "FGF 1 is the only FGF that can activate all FGF receptor
            splice variants"
  - term:
      id: GO:0018108
      label: peptidyl-tyrosine phosphorylation
    evidence_type: IDA
    original_reference_id: PMID:15629145
    review:
      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.
      action: ACCEPT
      reason: >-
        Direct demonstration of FGFR2 tyrosine kinase activity phosphorylating
        substrates. Core enzymatic function of receptor tyrosine kinases.
      supported_by:
        - reference_id: PMID:15629145
          supporting_text: "tyrosine 769 is required for the binding to KGFR and tyrosine
            phosphorylation of PLCgamma...through the regulation of FRS2 tyrosine
            phosphorylation"
  - term:
      id: GO:0018108
      label: peptidyl-tyrosine phosphorylation
    evidence_type: IDA
    original_reference_id: PMID:16844695
    review:
      summary: >-
        PMID:16844695 showed FGFR2 phosphorylates itself and downstream substrates.
        Both wild-type and mutant FGFR2 exhibit tyrosine phosphorylation activity.
      action: ACCEPT
      reason: >-
        Confirms FGFR2 tyrosine kinase activity in phosphorylating substrates.
      supported_by:
        - reference_id: PMID:16844695
          supporting_text: 2006 Jul 14. Intracellular retention, degradation, 
            and signaling of glycosylation-deficient FGFR2 and craniosynostosis 
            syndrome-associated FGFR2C278F.
  - term:
      id: GO:0033688
      label: regulation of osteoblast proliferation
    evidence_type: TAS
    original_reference_id: PMID:15190072
    review:
      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.
      action: ACCEPT
      reason: >-
        Direct evidence that FGFR2 regulates osteoblast proliferation. This function
        is highly relevant to craniosynostosis syndromes caused by FGFR2 mutations.
      supported_by:
        - reference_id: PMID:15190072
          supporting_text: "Fibroblast growth factors (FGFs) play an important regulatory
            role in skeletal development and bone formation"
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: IPI
    original_reference_id: PMID:16844695
    review:
      summary: >-
        PMID:16844695 studied FGFR2 homodimerization which is required for receptor
        activation. FGFR2 dimerizes upon ligand binding or constitutively in
        gain-of-function mutants.
      action: ACCEPT
      reason: >-
        FGFR2 homodimerization is essential for receptor activation. Documented
        by immunoprecipitation studies. Core mechanism of receptor activation.
      supported_by:
        - reference_id: PMID:16844695
          supporting_text: 2006 Jul 14. Intracellular retention, degradation, 
            and signaling of glycosylation-deficient FGFR2 and craniosynostosis 
            syndrome-associated FGFR2C278F.
  - term:
      id: GO:0043410
      label: positive regulation of MAPK cascade
    evidence_type: IMP
    original_reference_id: PMID:15629145
    review:
      summary: >-
        PMID:15629145 showed that KGFR Y769F mutation impairs MAPK activation,
        demonstrating that functional FGFR2 signaling is required for full MAPK
        cascade activation.
      action: ACCEPT
      reason: >-
        Mutant phenotype analysis confirms FGFR2 activates MAPK cascade. Core
        downstream signaling pathway.
      supported_by:
        - reference_id: PMID:15629145
          supporting_text: "tyrosine 769 is required...for the full activation of
            MAPKs"
  - term:
      id: GO:0045667
      label: regulation of osteoblast differentiation
    evidence_type: TAS
    original_reference_id: PMID:15190072
    review:
      summary: >-
        PMID:15190072 demonstrated that constitutive FGFR2 activation promotes
        osteoblast differentiation through Cbl-mediated degradation of Src family
        kinases Lyn and Fyn.
      action: ACCEPT
      reason: >-
        Direct evidence that FGFR2 regulates osteoblast differentiation. The
        FGFR2 S252W mutation (Apert syndrome) increases ALP expression, a marker
        of osteoblast differentiation.
      supported_by:
        - reference_id: PMID:15190072
          supporting_text: "constitutive FGFR2 activation induces c-Cbl-dependent
            Lyn and Fyn proteasome degradation, resulting in...increased ALP expression"
  - term:
      id: GO:0046777
      label: protein autophosphorylation
    evidence_type: IDA
    original_reference_id: PMID:15629145
    review:
      summary: >-
        PMID:15629145 demonstrated KGFR (FGFR2IIIb) autophosphorylation on tyrosine
        residues including Y769 upon ligand binding.
      action: ACCEPT
      reason: >-
        Direct demonstration of FGFR2 autophosphorylation. Core mechanism of
        receptor tyrosine kinase activation.
      supported_by:
        - reference_id: PMID:15629145
          supporting_text: "KGFR is rapidly autophosphorylated on specific tyrosine
            residues in the intracellular domain"
  - term:
      id: GO:0048705
      label: skeletal system morphogenesis
    evidence_type: TAS
    original_reference_id: PMID:15190072
    review:
      summary: >-
        PMID:15190072 discusses FGFR2 role in skeletal development. FGFR2 mutations
        cause skeletal abnormalities including craniosynostosis.
      action: ACCEPT
      reason: >-
        FGFR2 is essential for skeletal system development. Mutations cause
        multiple craniosynostosis syndromes affecting skull development.
      supported_by:
        - reference_id: PMID:15190072
          supporting_text: "Fibroblast growth factors (FGFs) play an important regulatory
            role in skeletal development and bone formation"
  - term:
      id: GO:0035602
      label: fibroblast growth factor receptor signaling pathway involved in 
        negative regulation of apoptotic process in bone marrow cell
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation transferred from mouse ortholog. Overly specific term for
        a context-dependent function that is not a primary role for human FGFR2.
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:0035603
      label: fibroblast growth factor receptor signaling pathway involved in 
        hemopoiesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation transferred from mouse ortholog. Hemopoiesis is not a primary
        function of FGFR2; this likely reflects pleiotropic effects in mouse models.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        FGFR2 primary functions are in epithelial-mesenchymal signaling, skeletal
        development, and wound healing. Hemopoietic role is not a core function.
  - term:
      id: GO:0035604
      label: fibroblast growth factor receptor signaling pathway involved in 
        positive regulation of cell proliferation in bone marrow
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation transferred from mouse ortholog. Overly specific term for
        bone marrow context that is not a primary FGFR2 function.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        While FGFR2 promotes proliferation generally, this bone marrow-specific
        context is not a core function for human FGFR2.
  - term:
      id: GO:0035607
      label: fibroblast growth factor receptor signaling pathway involved in 
        orbitofrontal cortex development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 has roles in brain development
        but this specific term for orbitofrontal cortex is highly specialized.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0021769
      label: orbitofrontal cortex development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for orbitofrontal cortex development.
        Related to the above signaling pathway annotation.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specialized developmental context. FGFR2 contributes to brain development
        but this specific region is not a core function.
  - term:
      id: GO:0021847
      label: ventricular zone neuroblast division
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for neural progenitor division in the
        ventricular zone during brain development.
      action: KEEP_AS_NON_CORE
      reason: >-
        FGF signaling has roles in neural development but this is a specialized
        developmental function, not a core FGFR2 function.
  - term:
      id: GO:0021860
      label: pyramidal neuron development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for pyramidal neuron development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specialized neuronal development context. Not a primary FGFR2 function.
  - term:
      id: GO:0045787
      label: positive regulation of cell cycle
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 promotes cell proliferation which
        involves positive regulation of the cell cycle.
      action: ACCEPT
      reason: >-
        Consistent with FGFR2 role in promoting cell proliferation. Mitogenic
        signaling through FRS2/MAPK pathway drives cell cycle progression.
  - term:
      id: GO:0060076
      label: excitatory synapse
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog suggesting FGFR2 localization at
        excitatory synapses. Unusual localization for a growth factor receptor.
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Indirect effect of FGFR2 signaling
        on transcription through downstream pathways.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0001525
      label: angiogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Duplicate of IBA annotation - FGF
        signaling has documented roles in angiogenesis.
      action: KEEP_AS_NON_CORE
      reason: >-
        Consistent with IBA annotation. Angiogenesis is a documented but non-core
        function for FGFR2; FGFR1 may be more prominent in vascular biology.
  - term:
      id: GO:0001657
      label: ureteric bud development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 has roles in kidney development
        including ureteric bud branching morphogenesis.
      action: KEEP_AS_NON_CORE
      reason: >-
        UniProt notes FGFR2 is required for normal embryonic patterning including
        organogenesis. Kidney development is a documented but tissue-specific
        developmental function.
  - term:
      id: GO:0001701
      label: in utero embryonic development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 is required for normal embryonic
        development as evidenced by embryonic lethality in knockout mice.
      action: KEEP_AS_NON_CORE
      reason: >-
        Very broad developmental term. FGFR2 is essential for development but
        more specific terms (limb, lung, skeletal) better capture core functions.
  - term:
      id: GO:0002053
      label: positive regulation of mesenchymal cell proliferation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2IIIc (mesenchymal isoform) promotes
        mesenchymal cell proliferation in response to FGF2/4 from epithelium.
      action: ACCEPT
      reason: >-
        Core function for FGFR2IIIc isoform. Mesenchymal proliferation is central
        to epithelial-mesenchymal signaling that FGFR2 mediates in development.
  - term:
      id: GO:0003148
      label: outflow tract septum morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Cardiac outflow tract development
        involves FGFR signaling but is a specialized developmental context.
      action: KEEP_AS_NON_CORE
      reason: >-
        Cardiac development role is documented for FGFRs but this specific
        structure is not a core FGFR2 function.
  - term:
      id: GO:0003149
      label: membranous septum morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Cardiac septum development is a
        specialized developmental context.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specialized cardiac developmental function, not a core FGFR2 function.
  - term:
      id: GO:0007267
      label: cell-cell signaling
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 mediates paracrine signaling
        between epithelium and mesenchyme.
      action: ACCEPT
      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.
  - term:
      id: GO:0007409
      label: axonogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGF signaling has roles in axon
        guidance and neuronal development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Neural development role is documented but not a primary FGFR2 function.
        More specialized than core epithelial-mesenchymal signaling roles.
  - term:
      id: GO:0008589
      label: regulation of smoothened signaling pathway
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Cross-talk between FGF and Hedgehog
        (Smoothened) pathways has been reported in development.
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:0009791
      label: post-embryonic development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 has roles in tissue homeostasis
        and repair after embryonic development.
      action: KEEP_AS_NON_CORE
      reason: >-
        FGFR2 continues to function in adult tissue homeostasis and wound healing
        but this is a broad term. Embryonic roles are better documented.
  - term:
      id: GO:0009880
      label: embryonic pattern specification
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 contributes to embryonic patterning
        through epithelial-mesenchymal interactions.
      action: ACCEPT
      reason: >-
        UniProt confirms FGFR2 is required for normal embryonic patterning. FGF
        signaling through FGFR2 establishes tissue boundaries and patterns during
        development.
  - term:
      id: GO:0009887
      label: animal organ morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 is required for morphogenesis
        of multiple organs including limbs, lungs, and skeleton.
      action: ACCEPT
      reason: >-
        Core developmental function. FGFR2 is essential for branching morphogenesis
        and organ development, particularly lungs, limbs, and craniofacial skeleton.
  - term:
      id: GO:0016331
      label: morphogenesis of embryonic epithelium
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2IIIb is expressed in epithelium
        and receives signals from mesenchyme to direct epithelial morphogenesis.
      action: ACCEPT
      reason: >-
        Core function for FGFR2IIIb isoform. Epithelial morphogenesis through
        FGF7/10 signaling is a primary developmental role.
  - term:
      id: GO:0022612
      label: gland morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 is required for salivary gland,
        lacrimal gland, and other gland development through branching morphogenesis.
      action: ACCEPT
      reason: >-
        Core developmental function. FGFR2-mediated branching morphogenesis is
        essential for gland development in multiple organ systems.
  - term:
      id: GO:0030177
      label: positive regulation of Wnt signaling pathway
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Cross-talk between FGF and Wnt pathways
        occurs during development but this is indirect signaling.
      action: KEEP_AS_NON_CORE
      reason: >-
        FGF-Wnt pathway interactions exist during development but positive regulation
        of Wnt signaling is not a direct core function of FGFR2.
  - term:
      id: GO:0030282
      label: bone mineralization
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 regulates osteoblast differentiation
        and bone development; mineralization is a downstream effect.
      action: KEEP_AS_NON_CORE
      reason: >-
        Indirect effect of FGFR2 on osteoblast function. The core function is
        regulating osteoblast proliferation/differentiation rather than
        mineralization per se.
  - term:
      id: GO:0030324
      label: lung development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 is essential for lung branching
        morphogenesis. UniProt confirms role in lung morphogenesis.
      action: ACCEPT
      reason: >-
        Core developmental function. FGFR2 (particularly IIIb/KGFR) is essential
        for lung epithelial branching morphogenesis through FGF10 signaling.
  - term:
      id: GO:0030855
      label: epithelial cell differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2IIIb in epithelial cells regulates
        their differentiation in response to mesenchymal FGF signals.
      action: ACCEPT
      reason: >-
        Core function for FGFR2IIIb isoform. Epithelial differentiation is directed
        by FGF7/10 signaling through the epithelial FGFR2 isoform.
  - term:
      id: GO:0030901
      label: midbrain development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for midbrain development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Brain development is one of many developmental contexts where FGFR2
        functions, but not a primary function.
  - term:
      id: GO:0030916
      label: otic vesicle formation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for inner ear development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specialized developmental context. FGFR2 contributes to ear development
        but this is not a core function.
  - term:
      id: GO:0031069
      label: hair follicle morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 is required for skin development
        including hair follicles. UniProt notes role in skin development.
      action: ACCEPT
      reason: >-
        Documented role in skin development. FGF signaling through FGFR2IIIb
        contributes to epithelial appendage formation including hair follicles.
  - term:
      id: GO:0032808
      label: lacrimal gland development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Lacrimal gland develops through
        branching morphogenesis requiring FGFR2 signaling.
      action: KEEP_AS_NON_CORE
      reason: >-
        Example of gland morphogenesis role. More general gland morphogenesis
        term already captures this function.
  - term:
      id: GO:0035265
      label: organ growth
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 promotes cell proliferation
        which contributes to organ growth during development.
      action: ACCEPT
      reason: >-
        General term consistent with FGFR2 role in promoting proliferation
        during organ development.
  - term:
      id: GO:0042472
      label: inner ear morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for inner ear development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specialized developmental context for ear morphogenesis.
  - term:
      id: GO:0042476
      label: odontogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGF signaling is involved in tooth
        development through epithelial-mesenchymal interactions.
      action: KEEP_AS_NON_CORE
      reason: >-
        Tooth development involves FGFR2 but is a specialized developmental
        context rather than a core function.
  - term:
      id: GO:0045165
      label: cell fate commitment
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 signaling influences cell fate
        decisions during development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Broad developmental term. FGFR2 influences cell fate but more specific
        terms better capture its functions.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 signaling can activate
        transcription through MAPK pathway and transcription factors.
      action: KEEP_AS_NON_CORE
      reason: >-
        Indirect downstream effect of FGFR2 signaling rather than a core
        molecular function of the receptor.
  - term:
      id: GO:0048286
      label: lung alveolus development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Specific aspect of lung development
        where FGFR2 contributes to alveolar formation.
      action: ACCEPT
      reason: >-
        Part of core lung development function. FGFR2 is essential for lung
        morphogenesis including alveolar development.
  - term:
      id: GO:0048557
      label: embryonic digestive tract morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for GI tract development.
      action: KEEP_AS_NON_CORE
      reason: >-
        One of many organs where FGFR2 contributes to development but not
        a primary documented function.
  - term:
      id: GO:0048562
      label: embryonic organ morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. General term for FGFR2 role in
        organ development during embryogenesis.
      action: ACCEPT
      reason: >-
        Core developmental function. FGFR2 is essential for morphogenesis of
        multiple organs through epithelial-mesenchymal interactions.
  - term:
      id: GO:0048565
      label: digestive tract development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for GI tract development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Digestive tract development is one of many developmental contexts.
  - term:
      id: GO:0048568
      label: embryonic organ development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Broad term for embryonic
        organogenesis role of FGFR2.
      action: ACCEPT
      reason: >-
        Core developmental function consistent with FGFR2 role in multiple
        organ systems during development.
  - term:
      id: GO:0048608
      label: reproductive structure development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for reproductive organ development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specialized developmental context not emphasized in human FGFR2 function.
  - term:
      id: GO:0048730
      label: epidermis morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 is required for skin
        development. UniProt confirms role in skin development.
      action: ACCEPT
      reason: >-
        Documented function. FGFR2IIIb in keratinocytes responds to FGF7/KGF
        from dermal fibroblasts to regulate epidermis.
  - term:
      id: GO:0048755
      label: branching morphogenesis of a nerve
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for nerve branching.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specialized neural context not a primary FGFR2 function.
  - term:
      id: GO:0048762
      label: mesenchymal cell differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2IIIc in mesenchyme responds
        to epithelial FGFs to promote mesenchymal differentiation.
      action: ACCEPT
      reason: >-
        Core function for FGFR2IIIc isoform. Mesenchymal differentiation is
        central to FGFR2 role in development.
  - term:
      id: GO:0050679
      label: positive regulation of epithelial cell proliferation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2IIIb promotes epithelial cell
        proliferation in response to FGF7/10. UniProt confirms proliferation
        in keratinocytes.
      action: ACCEPT
      reason: >-
        Core function for FGFR2IIIb isoform. Epithelial proliferation is a
        primary response to FGF7/10 signaling.
  - term:
      id: GO:0051150
      label: regulation of smooth muscle cell differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for smooth muscle differentiation.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specialized context for FGFR2 function in mesenchymal differentiation.
  - term:
      id: GO:0051781
      label: positive regulation of cell division
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 promotes cell proliferation
        which involves cell division.
      action: ACCEPT
      reason: >-
        Consistent with core mitogenic function of FGFR2 signaling.
  - term:
      id: GO:0055010
      label: ventricular cardiac muscle tissue morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for cardiac development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Cardiac development context is not a primary FGFR2 function.
  - term:
      id: GO:0060045
      label: positive regulation of cardiac muscle cell proliferation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for cardiac muscle proliferation.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specialized cardiac context not a primary FGFR2 function.
  - term:
      id: GO:0060174
      label: limb bud formation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 is essential for limb bud
        development. UniProt confirms role in limb bud development.
      action: ACCEPT
      reason: >-
        Core developmental function. FGFR2 is required for limb bud outgrowth
        and patterning through FGF signaling.
  - term:
      id: GO:0060348
      label: bone development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 is essential for bone
        development; mutations cause craniosynostosis syndromes.
      action: ACCEPT
      reason: >-
        Core developmental function. FGFR2 mutations in humans cause multiple
        skeletal syndromes demonstrating essential role in osteogenesis.
  - term:
      id: GO:0060349
      label: bone morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 regulates bone shape through
        effects on osteoblast function.
      action: ACCEPT
      reason: >-
        Core function evidenced by craniosynostosis syndromes where FGFR2
        mutations cause abnormal skull bone morphology.
  - term:
      id: GO:0060442
      label: branching involved in prostate gland morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Prostate gland develops through
        branching morphogenesis involving FGFR2.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specific example of branching morphogenesis. General gland morphogenesis
        term captures this function.
  - term:
      id: GO:0060445
      label: branching involved in salivary gland morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Salivary gland develops through
        FGFR2-dependent branching morphogenesis.
      action: ACCEPT
      reason: >-
        Well-documented example of FGFR2-dependent branching morphogenesis.
        FGF10/FGFR2IIIb signaling is essential for salivary gland development.
  - term:
      id: GO:0060449
      label: bud elongation involved in lung branching
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Specific aspect of lung branching
        morphogenesis involving bud outgrowth.
      action: ACCEPT
      reason: >-
        Core lung development function. FGF10/FGFR2IIIb signaling drives
        epithelial bud elongation in lung branching.
  - term:
      id: GO:0060463
      label: lung lobe morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for lung lobe formation.
      action: ACCEPT
      reason: >-
        Part of core lung development function of FGFR2.
  - term:
      id: GO:0060484
      label: lung-associated mesenchyme development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2IIIc in lung mesenchyme
        responds to epithelial FGFs during development.
      action: ACCEPT
      reason: >-
        Core lung development function. Both epithelial (IIIb) and mesenchymal
        (IIIc) FGFR2 isoforms contribute to lung development.
  - term:
      id: GO:0060501
      label: positive regulation of epithelial cell proliferation involved in 
        lung morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGF10/FGFR2IIIb signaling promotes
        lung epithelial proliferation during branching morphogenesis.
      action: ACCEPT
      reason: >-
        Core function for lung development. FGFR2IIIb-mediated epithelial
        proliferation is essential for lung morphogenesis.
  - term:
      id: GO:0060512
      label: prostate gland morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for prostate development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specific gland development context. More general gland morphogenesis
        captures this function.
  - term:
      id: GO:0060523
      label: prostate epithelial cord elongation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for prostate development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Specific prostate developmental context. More general epithelial
        morphogenesis and gland development terms capture this function.
  - term:
      id: GO:0060527
      label: prostate epithelial cord arborization involved in prostate 
        glandular acinus morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for highly specific prostate morphogenesis.
      action: KEEP_AS_NON_CORE
      reason: >-
        Overly specific developmental term. General gland morphogenesis captures
        FGFR2 role without this level of specificity.
  - term:
      id: GO:0060529
      label: squamous basal epithelial stem cell differentiation involved in 
        prostate gland acinus development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for very specific prostate stem cell context.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Extremely specific term that goes beyond core FGFR2 function. This level
        of specificity is not a primary FGFR2 function.
  - term:
      id: GO:0060601
      label: lateral sprouting from an epithelium
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Epithelial sprouting is part of
        branching morphogenesis that FGFR2 mediates.
      action: ACCEPT
      reason: >-
        Consistent with FGFR2 role in branching morphogenesis. Lateral sprouting
        is a core mechanism of epithelial branching in lungs and glands.
  - term:
      id: GO:0060615
      label: mammary gland bud formation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Mammary gland develops through
        FGFR2-dependent mechanisms similar to other glands.
      action: KEEP_AS_NON_CORE
      reason: >-
        Example of gland morphogenesis. General gland development terms capture
        this function.
  - term:
      id: GO:0060664
      label: epithelial cell proliferation involved in salivary gland 
        morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGF10/FGFR2IIIb signaling promotes
        epithelial proliferation in salivary gland development.
      action: ACCEPT
      reason: >-
        Core function for salivary gland development which is a well-documented
        FGFR2 function through epithelial-mesenchymal interactions.
  - term:
      id: GO:0060667
      label: branch elongation involved in salivary gland morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Branch elongation is a key aspect
        of salivary gland branching morphogenesis.
      action: ACCEPT
      reason: >-
        Core salivary gland development function. Consistent with FGFR2 role
        in branching morphogenesis.
  - term:
      id: GO:0060670
      label: branching involved in labyrinthine layer morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog for placental labyrinthine layer.
      action: KEEP_AS_NON_CORE
      reason: >-
        Placental development context. UniProt notes trophoblast function but
        this specific aspect is not emphasized.
  - term:
      id: GO:0060688
      label: regulation of morphogenesis of a branching structure
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 is a key regulator of branching
        morphogenesis in multiple organs.
      action: ACCEPT
      reason: >-
        Core developmental function. FGFR2 regulates branching morphogenesis in
        lungs, glands, and other organs through epithelial-mesenchymal signaling.
  - term:
      id: GO:0060915
      label: mesenchymal cell differentiation involved in lung development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2IIIc in lung mesenchyme responds
        to epithelial signals to regulate mesenchymal differentiation.
      action: ACCEPT
      reason: >-
        Core lung development function. Both epithelial (IIIb) and mesenchymal
        (IIIc) FGFR2 isoforms contribute to lung development.
  - term:
      id: GO:0060916
      label: mesenchymal cell proliferation involved in lung development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2IIIc in lung mesenchyme promotes
        proliferation in response to epithelial FGFs.
      action: ACCEPT
      reason: >-
        Core lung development function for FGFR2IIIc isoform.
  - term:
      id: GO:0070372
      label: regulation of ERK1 and ERK2 cascade
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 activates ERK1/2 (MAPK3/MAPK1)
        through the RAS-MAPK pathway.
      action: ACCEPT
      reason: >-
        Core signaling function. ERK1/2 cascade activation is a primary downstream
        effect of FGFR2 signaling through FRS2/GRB2/SOS/RAS pathway.
  - term:
      id: GO:0070374
      label: positive regulation of ERK1 and ERK2 cascade
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. FGFR2 positively regulates ERK1/2
        cascade activation.
      action: ACCEPT
      reason: >-
        Core signaling function. More specific child term of MAPK cascade
        regulation that is well-documented for FGFR2.
  - term:
      id: GO:0090263
      label: positive regulation of canonical Wnt signaling pathway
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation from mouse ortholog. Cross-talk between FGF and Wnt
        pathways occurs during development.
      action: KEEP_AS_NON_CORE
      reason: >-
        Indirect pathway cross-talk rather than a direct core function of FGFR2.
        More specific than general Wnt regulation annotation already reviewed.
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: NAS
    original_reference_id: PMID:8676562
    review:
      summary: >-
        NAS annotation for membrane localization. FGFR2 is a transmembrane
        receptor.
      action: ACCEPT
      reason: >-
        Correct but general term. More specific plasma membrane annotations exist.
      supported_by:
        - reference_id: PMID:8676562
          supporting_text: 'Apert syndrome, acrocephalosyndactyly Type I, is an autosomal
            dominant craniosynostosis comprising acrocephaly, facial dysmorphism and
            severe syndactyly of the hands and feet.'
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:17471512
    review:
      summary: >-
        PMID:17471512 demonstrated nuclear localization of FGF-10 receptor
        (FGFR2IIIb) in urothelial cells along with its ligand FGF-10.
      action: KEEP_AS_NON_CORE
      reason: >-
        Nuclear localization represents a specialized signaling mechanism rather
        than the primary localization. Main FGFR2 function is at plasma membrane.
      supported_by:
        - reference_id: PMID:17471512
          supporting_text: "The FGF-10 receptor was observed in cell nuclei regardless
            of the presence or concentration of exogenous rFGF-10 ligand"
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:17471512
    review:
      summary: >-
        PMID:17471512 showed FGF-10 receptor (FGFR2IIIb) localizes to cytoplasm
        in urothelial cells during trafficking.
      action: ACCEPT
      reason: >-
        FGFR2 is found in cytoplasm during biosynthesis, trafficking, and after
        internalization.
      supported_by:
        - reference_id: PMID:17471512
          supporting_text: "rFGF-10(no NLS) was found in cytoplasm to a far greater
            degree than rFGF-10"
  - term:
      id: GO:0005938
      label: cell cortex
    evidence_type: IDA
    original_reference_id: PMID:17471512
    review:
      summary: >-
        PMID:17471512 may have observed FGFR2 at the cell cortex during trafficking
        or at the plasma membrane interface.
      action: KEEP_AS_NON_CORE
      reason: >-
        Cell cortex localization is not a primary FGFR2 localization. May represent
        trafficking intermediate or plasma membrane-associated pool.
      supported_by:
        - reference_id: PMID:17471512
          supporting_text: Translocation of fibroblast growth factor-10 and its 
            receptor into nuclei of human urothelial cells.
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: IGI
    original_reference_id: PMID:8663044
    review:
      summary: >-
        IGI (Inferred from Genetic Interaction) annotation from PMID:8663044 which
        tested multiple FGF-FGFR combinations for mitogenic activity.
      action: ACCEPT
      reason: >-
        Consistent with core mitogenic function. PMID:8663044 demonstrated
        proliferative activity of FGFR2 with various FGF ligands.
      supported_by:
        - reference_id: PMID:8663044
          supporting_text: Receptor specificity of the fibroblast growth factor 
            family.
  - term:
      id: GO:0008543
      label: fibroblast growth factor receptor signaling pathway
    evidence_type: IGI
    original_reference_id: PMID:8663044
    review:
      summary: >-
        IGI annotation from PMID:8663044 demonstrating FGF receptor signaling
        through FGFR2.
      action: ACCEPT
      reason: >-
        Core biological process. PMID:8663044 is foundational study for FGFR
        signaling specificity.
      supported_by:
        - reference_id: PMID:8663044
          supporting_text: Receptor specificity of the fibroblast growth factor 
            family.
  - term:
      id: GO:0005007
      label: fibroblast growth factor receptor activity
    evidence_type: IGI
    original_reference_id: PMID:10830168
    review:
      summary: >-
        IGI annotation from PMID:10830168 which determined crystal structures
        of FGF-FGFR complexes and characterized ligand-receptor specificity.
      action: ACCEPT
      reason: >-
        Core molecular function. PMID:10830168 provided structural basis for
        FGF receptor specificity through alternative splicing.
      supported_by:
        - reference_id: PMID:10830168
          supporting_text: "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"
  - term:
      id: GO:0008543
      label: fibroblast growth factor receptor signaling pathway
    evidence_type: IPI
    original_reference_id: PMID:10830168
    review:
      summary: >-
        IPI annotation from PMID:10830168 based on physical interaction studies
        of FGF-FGFR complexes.
      action: ACCEPT
      reason: >-
        Core signaling pathway. Crystal structures revealed basis for ligand
        binding and receptor activation.
      supported_by:
        - reference_id: PMID:10830168
          supporting_text: Crystal structures of two FGF-FGFR complexes reveal 
            the determinants of ligand-receptor specificity.
  - term:
      id: GO:0017134
      label: fibroblast growth factor binding
    evidence_type: IPI
    original_reference_id: PMID:8386828
    review:
      summary: >-
        IPI annotation from PMID:8386828 demonstrating FGF-5 binding to FGFR2.
        Competition binding studies showed KD of 0.5-1.5 nM.
      action: ACCEPT
      reason: >-
        Core molecular function. Direct binding assays demonstrated FGF binding
        to FGFR2 with high affinity.
      supported_by:
        - reference_id: PMID:8386828
          supporting_text: "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"
  - term:
      id: GO:0005007
      label: fibroblast growth factor receptor activity
    evidence_type: NAS
    original_reference_id: PMID:8676562
    review:
      summary: >-
        NAS annotation for FGF receptor activity. Duplicate annotation with
        different evidence code.
      action: ACCEPT
      reason: >-
        Core molecular function supported by multiple evidence types.
      supported_by:
        - reference_id: PMID:8676562
          supporting_text: 'Apert syndrome, acrocephalosyndactyly Type I, is an autosomal
            dominant craniosynostosis comprising acrocephaly, facial dysmorphism and
            severe syndactyly of the hands and feet.'
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: NAS
    original_reference_id: PMID:1697263
    review:
      summary: >-
        NAS annotation for protein tyrosine kinase activity. FGFR2 is a receptor
        tyrosine kinase.
      action: ACCEPT
      reason: >-
        Core molecular function. FGFR2 is a well-characterized receptor tyrosine
        kinase (EC 2.7.10.1).
      supported_by:
        - reference_id: PMID:1697263
          supporting_text: Cloning and expression of two distinct high-affinity 
            receptors cross-reacting with acidic and basic fibroblast growth 
            factors.
  - term:
      id: GO:0005007
      label: fibroblast growth factor receptor activity
    evidence_type: NAS
    original_reference_id: PMID:1400433
    review:
      summary: >-
        NAS annotation from PMID:1400433 which identified alternative splicing
        creating isoforms with different ligand specificities.
      action: ACCEPT
      reason: >-
        Core molecular function. PMID:1400433 was important for understanding
        isoform-specific FGF binding.
      supported_by:
        - reference_id: PMID:1400433
          supporting_text: A novel form of fibroblast growth factor receptor 2.
  - term:
      id: GO:0005007
      label: fibroblast growth factor receptor activity
    evidence_type: NAS
    original_reference_id: PMID:1697263
    review:
      summary: >-
        NAS annotation for FGF receptor activity. Duplicate with different reference.
      action: ACCEPT
      reason: >-
        Core molecular function.
      supported_by:
        - reference_id: PMID:1697263
          supporting_text: Cloning and expression of two distinct high-affinity 
            receptors cross-reacting with acidic and basic fibroblast growth 
            factors.
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: NAS
    original_reference_id: PMID:1697263
    review:
      summary: >-
        NAS annotation for membrane localization. FGFR2 is a single-pass type I
        membrane protein.
      action: ACCEPT
      reason: >-
        Correct but general term. More specific plasma membrane annotations exist.
      supported_by:
        - reference_id: PMID:1697263
          supporting_text: Cloning and expression of two distinct high-affinity 
            receptors cross-reacting with acidic and basic fibroblast growth 
            factors.
core_functions:
  - molecular_function:
      id: GO:0005007
      label: fibroblast growth factor receptor activity
    directly_involved_in:
      - id: GO:0008543
        label: fibroblast growth factor receptor signaling pathway
      - id: GO:0008284
        label: positive regulation of cell population proliferation
      - id: GO:0070374
        label: positive regulation of ERK1 and ERK2 cascade
      - id: GO:0060348
        label: bone development
      - id: GO:0060688
        label: regulation of morphogenesis of a branching structure
      - id: GO:0048701
        label: embryonic cranial skeleton morphogenesis
      - id: GO:0030324
        label: lung development
    locations:
      - id: GO:0005886
        label: plasma membrane
references:
  - id: file:human/FGFR2/FGFR2-deep-research-falcon.md
    title: Deep research report on FGFR2 function, signaling, and clinical relevance
    findings:
      - statement: >-
          FGFR2 is a plasma membrane receptor tyrosine kinase with Ig-like
          extracellular domains whose IIIb/IIIc isoform switching determines
          epithelial vs mesenchymal ligand specificity.
      - statement: >-
          Core signaling through FRS2/MAPK and PLCgamma pathways drives
          proliferation, differentiation, and branching morphogenesis in lungs,
          limbs, skeleton, and glands.
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
    findings: []
  - id: GO_REF:0000003
    title: Gene Ontology annotation based on Enzyme Commission mapping
    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:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    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: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:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:10618369
    title: Structural interactions of fibroblast growth factor receptor with its
      ligands.
    findings: []
  - id: PMID:10830168
    title: Crystal structures of two FGF-FGFR complexes reveal the determinants 
      of ligand-receptor specificity.
    findings: []
  - id: PMID:11390973
    title: Structural basis for fibroblast growth factor receptor 2 activation 
      in Apert syndrome.
    findings: []
  - id: PMID:12591959
    title: Structural basis by which alternative splicing confers specificity in
      fibroblast growth factor receptors.
    findings: []
  - id: PMID:1309608
    title: 'Determination of ligand-binding specificity by alternative splicing: two
      distinct growth factor receptors encoded by a single gene.'
    findings: []
  - id: PMID:1400433
    title: A novel form of fibroblast growth factor receptor 2. Alternative 
      splicing of the third immunoglobulin-like domain confers ligand binding 
      specificity.
    findings: []
  - id: PMID:15190072
    title: Cbl-mediated degradation of Lyn and Fyn induced by constitutive 
      fibroblast growth factor receptor-2 activation supports osteoblast 
      differentiation.
    findings: []
  - id: PMID:15629145
    title: Tyrosine 769 of the keratinocyte growth factor receptor is required 
      for receptor signaling but not endocytosis.
    findings: []
  - id: PMID:16597614
    title: FGF-10 and its receptor exhibit bidirectional paracrine targeting to 
      urothelial and smooth muscle cells in the lower urinary tract.
    findings: []
  - id: PMID:16844695
    title: Intracellular retention, degradation, and signaling of 
      glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated 
      FGFR2C278F.
    findings: []
  - id: PMID:1697263
    title: Cloning and expression of two distinct high-affinity receptors 
      cross-reacting with acidic and basic fibroblast growth factors.
    findings: []
  - id: PMID:17471512
    title: Translocation of fibroblast growth factor-10 and its receptor into 
      nuclei of human urothelial cells.
    findings: []
  - id: PMID:17959718
    title: Heparanase cleavage of perlecan heparan sulfate modulates FGF10 
      activity during ex vivo submandibular gland branching morphogenesis.
    findings: []
  - id: PMID:21412257
    title: MiR-125b, a microRNA downregulated in psoriasis, modulates 
      keratinocyte proliferation by targeting FGFR2.
    findings: []
  - id: PMID:22726438
    title: Inhibition of basal FGF receptor signaling by dimeric Grb2.
    findings: []
  - id: PMID:23597563
    title: Molecular mechanism of SSR128129E, an extracellularly acting, 
      small-molecule, allosteric inhibitor of FGF receptor signaling.
    findings: []
  - id: PMID:25241761
    title: Using an in situ proximity ligation assay to systematically profile 
      endogenous protein-protein interactions in a pathway network.
    findings: []
  - id: PMID:26267536
    title: Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer 
      Therapy.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the 
      human interactome.
    findings: []
  - id: PMID:35384245
    title: Physical and functional interactome atlas of human receptor tyrosine 
      kinases.
    findings: []
  - id: PMID:35922511
    title: A physical wiring diagram for the human immune system.
    findings: []
  - id: PMID:7874170
    title: Jackson-Weiss and Crouzon syndromes are allelic with mutations in 
      fibroblast growth factor receptor 2.
    findings: []
  - id: PMID:7987400
    title: Mutations in the fibroblast growth factor receptor 2 gene cause 
      Crouzon syndrome.
    findings: []
  - id: PMID:8386828
    title: Activation of fibroblast growth factor (FGF) receptors by recombinant
      human FGF-5.
    findings: []
  - id: PMID:8663044
    title: Receptor specificity of the fibroblast growth factor family.
    findings: []
  - id: PMID:8676562
    title: '[Nucleotide sequences at intron 6 and exon 7 junction of fibroblast growth
      factor receptor 2 and rapid mutational analysis in Apert syndrome].'
    findings: []
  - id: Reactome:R-HSA-109699
    title: PI3K-containing complexes phosphorylate PIP2 to PIP3
    findings: []
  - id: Reactome:R-HSA-190258
    title: FGFR2c binds to FGF
    findings: []
  - id: Reactome:R-HSA-190260
    title: FGFR2b binds to FGF
    findings: []
  - id: Reactome:R-HSA-190408
    title: Autocatalytic phosphorylation of FGFR2b
    findings: []
  - id: Reactome:R-HSA-190413
    title: Autocatalytic phosphorylation of FGFR2c
    findings: []
  - id: Reactome:R-HSA-2029983
    title: Dimerization of FGFR2 ligand-independent mutants
    findings: []
  - id: Reactome:R-HSA-2029984
    title: Autocatalytic phosphorylation of FGFR2 ligand-independent  mutants
    findings: []
  - id: Reactome:R-HSA-2029988
    title: Dimerization of overexpressed FGFR2
    findings: []
  - id: Reactome:R-HSA-2029989
    title: Autocatalytic phosphorylation of overexpressed FGFR2 variants
    findings: []
  - id: Reactome:R-HSA-2029992
    title: Tyrosine kinase inhibitors bind to overexpressed FGFR2 variants
    findings: []
  - id: Reactome:R-HSA-2033472
    title: FGFR2c mutants bind an expanded range of ligands
    findings: []
  - id: Reactome:R-HSA-2033474
    title: FGFR2b mutants bind an expanded range of ligands
    findings: []
  - id: Reactome:R-HSA-2033479
    title: Dimerization of FGFR2 point mutants with enhanced kinase activity
    findings: []
  - id: Reactome:R-HSA-2033486
    title: Autocatalytic phosphorylation of FGFR2c mutants with enhanced ligand 
      binding
    findings: []
  - id: Reactome:R-HSA-2033488
    title: Autocatalytic phosphorylation of FGFR2b mutants with enhanced ligand 
      binding
    findings: []
  - id: Reactome:R-HSA-2033490
    title: Autocatalytic phosphorylation of FGFR2 point mutants with enhanced 
      kinase activity
    findings: []
  - id: Reactome:R-HSA-2067713
    title: GP369 inhibits activation of amplified FGFR2 signaling
    findings: []
  - id: Reactome:R-HSA-2077424
    title: Point mutants of FGFR2 bind and are inactivated by tyrosine kinase 
      inhibitors
    findings: []
  - id: Reactome:R-HSA-2316434
    title: PI3K phosphorylates PIP2 to PIP3
    findings: []
  - id: Reactome:R-HSA-2400009
    title: PI3K inhibitors block PI3K catalytic activity
    findings: []
  - id: Reactome:R-HSA-5654147
    title: Activated FGFR2 phosphorylates PLCG1
    findings: []
  - id: Reactome:R-HSA-5654157
    title: p-4Y-PLCG1 dissociates from activated FGFR2
    findings: []
  - id: Reactome:R-HSA-5654159
    title: Activated FGFR2 binds PLCG1
    findings: []
  - id: Reactome:R-HSA-5654397
    title: Activated FGFR2 phosphorylates FRS2
    findings: []
  - id: Reactome:R-HSA-5654399
    title: Activated FGFR2 binds FRS2
    findings: []
  - id: Reactome:R-HSA-5654402
    title: Activated FGFR2:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
    findings: []
  - id: Reactome:R-HSA-5654404
    title: Activated FGFR2 binds SHC1
    findings: []
  - id: Reactome:R-HSA-5654406
    title: Activated FGFR2:p-SHC1 binds GRB2:SOS1
    findings: []
  - id: Reactome:R-HSA-5654407
    title: Activated FGFR2 phosphorylates SHC1
    findings: []
  - id: Reactome:R-HSA-5654562
    title: Activated ERK1/2 threonine-phosphorylates FGFR2-associated FRS2
    findings: []
  - id: Reactome:R-HSA-5654603
    title: Activated FGFR2 binds FRS3
    findings: []
  - id: Reactome:R-HSA-5654605
    title: Activated FGFR2 phosphorylates FRS3
    findings: []
  - id: Reactome:R-HSA-5654607
    title: Activated FGFR2 phosphorylates PPTN11
    findings: []
  - id: Reactome:R-HSA-5654608
    title: Activated FGFR2:p-FRS bind to PPTN11
    findings: []
  - id: Reactome:R-HSA-5654612
    title: Activated FGFR2:p-FRS2 binds GRB2:GAB1:PIK3R1
    findings: []
  - id: Reactome:R-HSA-5654614
    title: Activated FGFR2:p-FRS2:GRB2:GAB1:PI3KR1 binds PIK3CA
    findings: []
  - id: Reactome:R-HSA-5654615
    title: Activated FGFR2:pFRS binds GRB2:SOS1
    findings: []
  - id: Reactome:R-HSA-5654618
    title: Activated FGFR2:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
    findings: []
  - id: Reactome:R-HSA-5654620
    title: Activated FGFR2:p-FRS2:p-PPTN11 binds GRB2:GAB1:PI3KR1
    findings: []
  - id: Reactome:R-HSA-5654622
    title: Activated FGFR2:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1 binds PIK3CA
    findings: []
  - id: Reactome:R-HSA-5654677
    title: CBL ubiquitinates FRS2 and FGFR2
    findings: []
  - id: Reactome:R-HSA-5654697
    title: FGFR2- and PTPN11- associated PI3K phosphorylates PIP2 to PIP3
    findings: []
  - id: Reactome:R-HSA-5654701
    title: FGFR2-associated PI3K phosphorylates PIP2 to PIP3
    findings: []
  - id: Reactome:R-HSA-5654729
    title: p-CBL:GRB2 binds p-FRS2:activated FGFR2
    findings: []
  - id: Reactome:R-HSA-5654748
    title: p-4Y-PLCG1 dissociates from activated FGFR2 mutants
    findings: []
  - id: Reactome:R-HSA-5655233
    title: Activated FGFR2 mutants:p-FRS2 binds GRB2-SOS1
    findings: []
  - id: Reactome:R-HSA-5655241
    title: Activated FGFR2 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide 
      exchange
    findings: []
  - id: Reactome:R-HSA-5655245
    title: Activated FGFR2 mutants:p-FRS2:GRB2:GAB1:PIK3R1 binds PIK3CA
    findings: []
  - id: Reactome:R-HSA-5655268
    title: Activated FGFR2 mutants phosphorylate FRS2
    findings: []
  - id: Reactome:R-HSA-5655301
    title: Activated FGFR2 mutants phosphorylate PLCG1
    findings: []
  - id: Reactome:R-HSA-5655320
    title: Activated FGFR2 mutants:p-FRS2 binds GRB2:GAB1:PIK3R1
    findings: []
  - id: Reactome:R-HSA-5655323
    title: Activated FGFR2 mutant-associated PI3K phosphorylates PIP2 to PIP3
    findings: []
  - id: Reactome:R-HSA-5655339
    title: Activated FGFR2 mutants bind FRS2
    findings: []
  - id: Reactome:R-HSA-5655343
    title: Activated FGFR2 mutants bind PLCG1
    findings: []
  - id: Reactome:R-HSA-5672965
    title: RAS GEFs promote RAS nucleotide exchange
    findings: []
  - id: Reactome:R-HSA-8853313
    title: FGFR2 fusions autophosphorylate
    findings: []
  - id: Reactome:R-HSA-8853319
    title: FGFR2 fusions dimerize
    findings: []
  - id: Reactome:R-NUL-8853328
    title: Mouse FGFR2 IIIa TM binds FGF1,2 and full-length receptors
    findings: []