FGF7, also called keratinocyte growth factor (KGF), is a secreted, heparin-binding member of the fibroblast growth factor family (FGF7 subfamily with FGF3, FGF10 and FGF22). It is produced mainly by mesenchymal and stromal cells such as fibroblasts and acts in a paracrine manner on neighbouring epithelial cells. FGF7 binds with high selectivity to the epithelial IIIb splice isoform of FGFR2 (the KGF receptor), in complexes stabilized by heparan sulfate, triggering receptor tyrosine kinase activation and downstream RAS-MAPK, PI3K-AKT and PLC-gamma signalling. Its principal biological role is as a mitogen, survival and motility factor for epithelial cells, including epidermal keratinocytes, lung alveolar and airway epithelium and embryonic pancreatic epithelium, contributing to epithelial development, homeostasis and re-epithelialization after injury. In the mouse hippocampus, FGF7 released from pyramidal neuron dendrites also acts as a target-derived organizer of inhibitory presynaptic terminals. A truncated recombinant form (palifermin) is used clinically to protect oral mucosa during cytotoxic cancer therapy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005111 type 2 fibroblast growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: FGF7 is a selective ligand of the epithelial IIIb splice isoform of FGFR2 (the KGF receptor); type 2 FGF receptor binding is the precise, phylogenetically placed description of its receptor-binding activity. Reason: The PAINT node for the FGF7/FGF10 subfamily places FGFR2 binding at the right specificity. Direct binding data show KGFR (FGFR2 IIIb) is a high-affinity FGF7 receptor while the IIIc isoform does not bind it. This is the core molecular function. Supporting Evidence: PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. file:human/FGF7/FGF7-uniprot.txt Interacts with FGFR2. |
| GO:0005515 protein binding | IPI PMID:1309608 Determination of ligand-binding specificity by alternative s... | MODIFY | Summary: Binding assays identified FGF7 (KGF) as a high-affinity ligand of the FGFR2 IIIb isoform (KGFR, P21802-3), which is what the IntAct IPI row records. Reason: Generic protein binding is uninformative. The interacting partner is the FGFR2 IIIb receptor, so the informative term is type 2 fibroblast growth factor receptor binding (GO:0005111). The interaction itself is well supported. Proposed replacements: type 2 fibroblast growth factor receptor binding Supporting Evidence: PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. PMID:1309608 The KGFR transcript was specific to epithelial cells |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: FGF7 has a cleaved N-terminal signal peptide and is secreted by mesenchymal/stromal cells to act on neighbouring epithelia; the extracellular region is where it binds heparan sulfate and FGFR2b. Reason: Consistent with the family-level PAINT placement for canonical secreted FGFs and with direct purification of KGF from fibroblast conditioned medium. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:2915979 A growth factor specific for epithelial cells was identified in conditioned medium of a human embryonic lung fibroblast cell line. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Secreted localization derived from the UniProt subcellular location (SL-0243) mapping; correct for FGF7. Reason: FGF7 is secreted and acts extracellularly; the automatic mapping is consistent with experimental evidence. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-109699 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190260 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190408 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2033472 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2033474 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2033486 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2033488 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2077421 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2077424 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2316434 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2400009 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654147 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654157 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654159 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654397 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654399 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654402 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654404 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654406 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654407 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654562 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654603 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654605 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654607 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654608 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654612 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654614 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654615 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654618 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654620 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654622 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654677 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654697 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654701 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654729 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654748 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655233 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655241 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655245 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655268 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655301 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655320 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655323 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655339 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655343 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5656070 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: FGF7 is a secreted ligand; in this Reactome reaction it participates as the extracellular ligand bound to FGFR2b (wild-type or mutant) at the plasma membrane. This is one of many source-distinct Reactome rows for the same valid extracellular location. Reason: The extracellular region is correct for the ligand component of FGF-FGFR2b complexes. Retained as a valid, redundant location record. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | REMOVE | Summary: Propagated from the FGF-family root node (PTN000160075), whose cytoplasmic activity reflects intracellular FGFs and the non-signal-peptide FGF1/FGF2 rather than classically secreted ligands. Reason: FGF7 carries a cleaved signal peptide (residues 1-31), is secreted, and exerts its activity extracellularly on FGFR2b. There is no experimental evidence for a cytoplasmic site of action for human or mouse FGF7 (the mouse Fgf7 GO record has no experimental cytoplasm annotation). The node placement over-propagates an intracellular property of other clades to a secreted paracrine ligand. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000160075 SUPPORTS SOURCE BUT NOT TARGET FGF family root node; spans intracellular FGF homologous factors and signal-peptide-less FGF1/FGF2 as well as classically secreted paracrine FGFs. UniProtKB:Q92913 SUPPORTS SOURCE BUT NOT TARGET FGF13, an intracellular FGF homologous factor; cytoplasmic activity does not transfer to secreted FGF7. UniProtKB:P05230 SUPPORTS SOURCE BUT NOT TARGET FGF1 lacks a signal peptide and has intracellular pools; not representative of FGF7. UniProtKB:P09038 SUPPORTS SOURCE BUT NOT TARGET FGF2 lacks a signal peptide and has intracellular isoforms; not representative of FGF7. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:human/FGF7/FGF7-uniprot.txt SIGNAL 1..31 |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from mouse Fgf7 (IDA, PMID:12837279). As a secreted glycoprotein FGF7 necessarily transits the Golgi apparatus. Reason: Golgi localization is a biosynthetic transit compartment, not the site of FGF7 function; plausible but not informative for its role. Supporting Evidence: file:human/FGF7/FGF7-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:human/FGF7/FGF7-uniprot.txt CARBOHYD 45 |
| GO:0007165 signal transduction | NAS PMID:2475908 Human KGF is FGF-related with properties of a paracrine effe... | MODIFY | Summary: FGF7 initiates signalling by activating FGFR2b; the original author statement identified KGF as an FGF-related paracrine effector. Reason: Signal transduction is too general. FGF7 acts as the extracellular ligand of the FGF receptor signaling pathway, which is the informative process term (already supported by IBA and IGI rows). Proposed replacements: fibroblast growth factor receptor signaling pathway Supporting Evidence: PMID:2475908 The complementary DNA sequence of KGF demonstrates that it is a member of the fibroblast growth factor family. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0008083 growth factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: FGF7 is a classic polypeptide growth factor that activates a receptor tyrosine kinase to drive epithelial proliferation. Reason: Growth factor activity (a receptor ligand activity) is supported by the family PAINT placement and by direct mitogenic assays of purified KGF. Supporting Evidence: PMID:2915979 Purified KGF was a potent mitogen for epithelial cells, capable of stimulating DNA synthesis in quiescent BALB/MK epidermal keratinocytes by greater than 500-fold with activity detectable at 0.1 nM and maximal at 1.0 nM. |
| GO:0008083 growth factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro FGF family (IPR002209) mapping to growth factor activity; correct for FGF7. Reason: Consistent with experimental mitogenic activity of FGF7. Supporting Evidence: PMID:2915979 Purified KGF was a potent mitogen for epithelial cells, capable of stimulating DNA synthesis in quiescent BALB/MK epidermal keratinocytes by greater than 500-fold with activity detectable at 0.1 nM and maximal at 1.0 nM. |
| GO:0008083 growth factor activity | TAS PMID:2475908 Human KGF is FGF-related with properties of a paracrine effe... | ACCEPT | Summary: The KGF cDNA paper describes an FGF-related epithelial mitogen acting as a paracrine stromal effector. Reason: Growth factor activity is the defining molecular role of FGF7. Supporting Evidence: PMID:2475908 Keratinocyte growth factor (KGF) is a human mitogen that is specific for epithelial cells. PMID:2475908 The KGF transcript was present in stromal cells derived from epithelial tissues. |
| GO:0008284 positive regulation of cell population proliferation | IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family. | ACCEPT | Summary: FGF7 stimulated proliferation of BaF3 cells engineered to express FGFR2 splice variants in the FGF receptor-specificity survey (IGI with FGFR2). Reason: Mitogenic activity dependent on the FGFR2 receptor is directly measured in this assay system; the more specific epithelial term is captured separately. Supporting Evidence: PMID:8663044 To determine potentially relevant ligand-receptor pairs we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. file:human/FGF7/FGF7-uniprot.txt Growth factor active on keratinocytes. |
| GO:0008284 positive regulation of cell population proliferation | TAS PMID:2915979 Purification and characterization of a newly identified grow... | ACCEPT | Summary: Purified KGF was a potent mitogen for epithelial cells (keratinocytes) but not fibroblasts or endothelial cells. Reason: Correct: purified KGF is a potent mitogen. The effect is restricted to epithelial cells, which is captured more specifically by the positive regulation of epithelial cell proliferation annotations; this broader parent is retained for consistency with the IGI row. Supporting Evidence: PMID:2915979 Purified KGF was a potent mitogen for epithelial cells, capable of stimulating DNA synthesis in quiescent BALB/MK epidermal keratinocytes by greater than 500-fold with activity detectable at 0.1 nM and maximal at 1.0 nM. PMID:2915979 Lack of mitogenic activity on either fibroblasts or endothelial cells indicated that KGF possessed a target cell specificity distinct from any previously characterized growth factor. |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: FGF7 is an FGFR2b ligand that triggers receptor dimerization, autophosphorylation and FRS2-dependent downstream signalling. Reason: Core process: FGF7 participates as the activating ligand of the FGF receptor signaling pathway. PAINT placement for the whole FGF family is sound. Supporting Evidence: PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. file:human/FGF7/FGF7-deep-research-falcon.md The phosphorylated receptor recruits FRS2Ξ±, which associates with GRB2 and the guanine nucleotide exchange factor SOS, leading to RAS activation and subsequent RAF-MEK-ERK/MAPK signaling |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IGI PMID:8663044 Receptor specificity of the fibroblast growth factor family. | ACCEPT | Summary: Genetic interaction with FGFR2 in engineered BaF3 cells shows FGF7 activity requires FGFR2 (IIIb) signalling. Reason: Consistent with the core ligand role in FGFR signalling. Supporting Evidence: PMID:8663044 To determine potentially relevant ligand-receptor pairs we have engineered mitogenically responsive cell lines expressing the major splice variants of all the known FGF receptors. PMID:1309608 Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. |
| GO:0008544 epidermis development | TAS PMID:7973639 The function of KGF in morphogenesis of epithelium and reepi... | KEEP AS NON CORE | Summary: A dominant-negative KGF receptor in basal keratinocytes caused epidermal atrophy and hair follicle abnormalities. Reason: The dominant-negative FGFR2b blocks all FGFR2b ligands (FGF7, FGF10, FGF22 and others), so the phenotype is not attributable to FGF7 alone; FGF7 contributes to epidermal homeostasis as one paracrine mitogen. Retained as a non-core developmental/tissue role. Supporting Evidence: PMID:7973639 The skin of transgenic mice was characterized by epidermal atrophy, abnormalities in the hair follicles, and dermal hyperthickening. |
| GO:0009611 response to wounding | TAS PMID:7973639 The function of KGF in morphogenesis of epithelium and reepi... | KEEP AS NON CORE | Summary: Inhibition of KGF-receptor signalling in keratinocytes reduced wound-edge keratinocyte proliferation and delayed re-epithelialization. Reason: FGF7 is induced in wounds and promotes re-epithelialization, but the cited experiment perturbs the receptor (shared ligands) and Fgf7-deficient mice are reported to heal with limited defects due to redundancy. A valid, non-core tissue-repair role. Supporting Evidence: PMID:7973639 Upon skin injury, inhibition of KGF receptor signaling reduced the proliferation rate of epidermal keratinocytes at the wound edge, resulting in substantially delayed reepithelialization of the wound. |
| GO:0010463 mesenchymal cell proliferation | IDA PMID:11023837 alpha2-macroglobulin modulates the immunoregulatory function... | REMOVE | Summary: The cited paper (alpha2-macroglobulin and the lipocalin PP14/glycodelin in T-cell proliferation) does not concern FGF7. The full text (Biochem J 2000, PMC1221387; read from a PDF supplied by the reviewer) never mentions FGF7, KGF, keratinocyte growth factor, fibroblasts or mesenchymal cells; its only proliferation assay is a T-cell assay, and the only growth factors named are IL-2, TGF-beta, PDGF and NGF, in background on alpha2-macroglobulin as a carrier. FGF7 is classically characterized as lacking mitogenic activity on fibroblasts. Reason: The full text was checked and contains no FGF7 experiment, so the IDA is not supported by its reference and is most likely attached to a mis-entered PMID. The biology also argues against it, because FGF7 targets FGFR2b-expressing epithelia and does not stimulate fibroblast proliferation. UniProt should be notified so that the source of the original curation can be traced. Supporting Evidence: PMID:2915979 Lack of mitogenic activity on either fibroblasts or endothelial cells indicated that KGF possessed a target cell specificity distinct from any previously characterized growth factor. PMID:11023837 an interaction between PP14 and a major serum protein carrier, alpha(2)-macroglobulin (alpha(2)M), was documented for the first time. |
| GO:0010838 positive regulation of keratinocyte proliferation | IDA PMID:17449030 Cortactin involvement in the keratinocyte growth factor and ... | ACCEPT | Summary: KGF/FGF7 is the prototypic keratinocyte mitogen, acting through KGFR (FGFR2 IIIb). Reason: Keratinocyte proliferation is the eponymous and best-characterized FGF7 output, also shown with purified protein on epidermal keratinocytes (PMID:2915979). Supporting Evidence: PMID:17449030 Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10 (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (KGFR). PMID:2915979 Purified KGF was a potent mitogen for epithelial cells, capable of stimulating DNA synthesis in quiescent BALB/MK epidermal keratinocytes by greater than 500-fold with activity detectable at 0.1 nM and maximal at 1.0 nM. |
| GO:0022008 neurogenesis | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Propagated from the FGF-family root node on the basis of neurogenic FGFs (e.g. FGF2, FGF8 and relatives). Reason: FGF7 has no demonstrated role in generating neurons. Its documented neural function (mouse) is as a target-derived presynaptic organizer of inhibitory synapses, which is synapse maturation/organization, not neurogenesis. The family-root placement over-extends a property of other FGF subfamilies. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE GRANULARITY MISMATCH Sources checked: PANTHER:PTN000160075 SUPPORTS SOURCE BUT NOT TARGET FGF family root node; neurogenic roles belong to other subfamilies (e.g. FGF8, FGF2), not to the epithelial-directed FGF7 subfamily. UniProtKB:P55075 SUPPORTS SOURCE BUT NOT TARGET FGF8 neural patterning/neurogenesis role does not transfer to FGF7, whose neural role is inhibitory synapse organization. Supporting Evidence: PMID:20505669 FGF22 and FGF7, promote the organization of excitatory and inhibitory presynaptic terminals, respectively, as target-derived presynaptic organizers. |
| GO:0030036 actin cytoskeleton organization | IDA PMID:17449030 Cortactin involvement in the keratinocyte growth factor and ... | KEEP AS NON CORE | Summary: KGF induced lamellipodia/ruffle formation and cortical actin assembly in human keratinocytes via Src/PI3K-dependent cortactin phosphorylation. Reason: A real but downstream cellular response of FGFR2b-expressing keratinocytes; FGF7 acts upstream as the ligand. Supporting Evidence: PMID:17449030 KGF induces keratinocyte motility and cytoskeletal rearrangement PMID:17449030 Both growth factors promoted phosphorylation and subsequent membrane translocation of cortactin, an F-actin binding protein involved in cell migration |
| GO:0030324 lung development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FGF7 is expressed by lung mesenchyme and is a strong mitogen for lung epithelium; it also stimulates fetal lung liquid secretion. Reason: The PAINT node for the FGF7/FGF10 subfamily is reasonable, but Fgf7-null lungs are histologically normal (redundancy with FGF10), so lung development is a supporting tissue context rather than a core function. Supporting Evidence: PMID:9740653 BrdU incorporation analysis suggests that FGF-10, in contrast to FGF-7, is a modest proliferation factor for the lung epithelium. file:human/FGF7/FGF7-deep-research-falcon.md However, Fgf7 knockout mice have normal lung histology, indicating functional redundancy with other FGFs |
| GO:0030334 regulation of cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FGF7 stimulates keratinocyte motility; the FGF family PAINT node places regulation of cell migration broadly. Reason: Supported for FGF7 by keratinocyte migration experiments (PMID:17449030), but migration is a secondary output relative to epithelial proliferation. Supporting Evidence: PMID:17449030 KGF induces keratinocyte motility and cytoskeletal rearrangement PMID:17449030 siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. |
| GO:0034394 protein localization to cell surface | IDA PMID:17449030 Cortactin involvement in the keratinocyte growth factor and ... | MARK AS OVER ANNOTATED | Summary: Annotation reflects KGF-induced translocation of cortactin to the plasma membrane/cortical actin in keratinocytes. Reason: Cortactin is a cytoplasmic F-actin-binding protein that moves to the cell cortex, not to the cell surface; the effect is a remote downstream consequence of FGFR2b-Src/PI3K signalling rather than an FGF7 activity. The term overstates FGF7 involvement. Supporting Evidence: PMID:17449030 Both growth factors promoted phosphorylation and subsequent membrane translocation of cortactin, an F-actin binding protein involved in cell migration |
| GO:0042056 chemoattractant activity | IDA PMID:17449030 Cortactin involvement in the keratinocyte growth factor and ... | KEEP AS NON CORE | Summary: KGF promoted keratinocyte migration in migration assays; the curator interpreted this as chemoattractant activity. Reason: FGF7 is a motogen for keratinocytes, and the curator had access to the full text of the migration assays. Its defining molecular activity is receptor ligand/growth factor activity; the chemoattractant reading is retained as non-core. Supporting Evidence: PMID:17449030 KGF induces keratinocyte motility and cytoskeletal rearrangement PMID:17449030 siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. |
| GO:0043410 positive regulation of MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: FGF7 binding to FGFR2b activates the FRS2-GRB2-SOS-RAS-RAF-MEK-ERK cascade. Reason: Well-established downstream output of FGF ligand-receptor engagement; family PAINT placement is sound. Supporting Evidence: file:human/FGF7/FGF7-deep-research-falcon.md The phosphorylated receptor recruits FRS2Ξ±, which associates with GRB2 and the guanine nucleotide exchange factor SOS, leading to RAS activation and subsequent RAF-MEK-ERK/MAPK signaling |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred from mouse Fgf7 IDA (PMID:17394208), where FGF7 or FGF10 induced Elf5 expression in embryonic lung epithelium via FGFR2b-PI3K/AKT. Reason: Target-gene induction is a remote downstream consequence of receptor signalling; annotating a secreted ligand to positive regulation of DNA-templated transcription conveys little and is shared by every signalling ligand. Supporting Evidence: PMID:17394208 We found that expression of Elf5 was induced by FGF7 and FGF10, ligands that primarily bind FGFR2b. |
| GO:0050679 positive regulation of epithelial cell proliferation | IBA GO_REF:0000033 | ACCEPT | Summary: FGF7 is a mesenchyme-derived paracrine mitogen for FGFR2b-expressing epithelial cells. Reason: Core biological role, supported by the FGF7-subfamily PAINT node and by direct experiments in keratinocytes and embryonic pancreatic epithelium; the target appearing among its own donors reflects experimental grounding. Supporting Evidence: PMID:2915979 Purified KGF was a potent mitogen for epithelial cells, capable of stimulating DNA synthesis in quiescent BALB/MK epidermal keratinocytes by greater than 500-fold with activity detectable at 0.1 nM and maximal at 1.0 nM. PMID:15690149 human embryonic pancreatic mesenchyme expresses FGF7 and FGF10 that act on epithelial cells to activate their proliferation |
| GO:0050679 positive regulation of epithelial cell proliferation | IDA PMID:11493558 Haploinsufficiency of the forkhead gene Foxf1, a target for ... | ACCEPT | Summary: MGI annotation from lung organ-culture experiments in the Foxf1 haploinsufficiency study, in which FGF7 was applied to developing lung. Reason: The abstract reports FGF7 effects on lung Foxf1/Shh expression; the proliferation result is presumably in the full text seen by the curator. Epithelial mitogenesis is the canonical FGF7 activity, so the annotation is deferred to. Supporting Evidence: PMID:11493558 Fibroblast growth factor (FGF) 10 and FGF7 both decrease Foxf1 expression PMID:2915979 Purified KGF was a potent mitogen for epithelial cells, capable of stimulating DNA synthesis in quiescent BALB/MK epidermal keratinocytes by greater than 500-fold with activity detectable at 0.1 nM and maximal at 1.0 nM. |
| GO:0050679 positive regulation of epithelial cell proliferation | IDA PMID:15690149 Fibroblast growth factors 7 and 10 are expressed in the huma... | ACCEPT | Summary: Human embryonic pancreatic mesenchyme expresses FGF7, which induced proliferation (BrdU incorporation) of pancreatic epithelial cells in vitro. Reason: Direct human evidence for the core paracrine mesenchyme-to-epithelium mitogenic role. Supporting Evidence: PMID:15690149 human embryonic pancreatic mesenchyme expresses FGF7 and FGF10 that act on epithelial cells to activate their proliferation PMID:15690149 We next demonstrated that FGF7 and FGF10 were able to induce the proliferation of the epithelial cells in vitro. |
| GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation | IDA PMID:17449030 Cortactin involvement in the keratinocyte growth factor and ... | KEEP AS NON CORE | Summary: KGF stimulated Src-dependent tyrosine phosphorylation of cortactin in keratinocytes. Reason: Downstream of FGFR2b autophosphorylation and Src; a real but indirect consequence of FGF7 ligand activity. Supporting Evidence: PMID:17449030 Cortactin phosphorylation induced by both growth factors was Src-dependent |
| GO:0050918 positive chemotaxis | IDA PMID:17449030 Cortactin involvement in the keratinocyte growth factor and ... | KEEP AS NON CORE | Summary: KGF promoted directed keratinocyte migration. Reason: FGF7 is a keratinocyte motogen; the process is a response of the target cell to the ligand, retained as non-core relative to epithelial proliferation. Supporting Evidence: PMID:17449030 KGF induces keratinocyte motility and cytoskeletal rearrangement PMID:17449030 siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. |
| GO:0051549 positive regulation of keratinocyte migration | IDA PMID:17449030 Cortactin involvement in the keratinocyte growth factor and ... | KEEP AS NON CORE | Summary: KGF promoted keratinocyte migration more efficiently than FGF10; migration required cortactin, Src and PI3K. Reason: Well supported (migration assays, siRNA) and relevant to re-epithelialization, but secondary to the core mitogenic role. Supporting Evidence: PMID:17449030 KGF induces keratinocyte motility and cytoskeletal rearrangement PMID:17449030 siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. PMID:17449030 FGF10 is less efficient than KGF in promoting migration |
| GO:0060501 positive regulation of epithelial cell proliferation involved in lung morphogenesis | IDA PMID:9740653 FGF-10 is a chemotactic factor for distal epithelial buds du... | KEEP AS NON CORE | Summary: In embryonic lung cultures FGF7 was a strong proliferation factor for lung epithelium, in contrast to FGF10. Reason: A tissue-specific instance of the core epithelial mitogenic role; retained as non-core given Fgf7-null lungs develop normally. Supporting Evidence: PMID:9740653 BrdU incorporation analysis suggests that FGF-10, in contrast to FGF-7, is a modest proliferation factor for the lung epithelium. |
| GO:0061033 secretion by lung epithelial cell involved in lung growth | IDA PMID:10541313 KGF and FGF-10 stimulate liquid secretion in human fetal lun... | KEEP AS NON CORE | Summary: KGF induced dose-dependent increases in intraluminal volume (liquid secretion) in first-trimester human fetal lung explants. Reason: Direct human explant evidence; a tissue-specific physiological output downstream of FGFR2b signalling in lung epithelium. Supporting Evidence: PMID:10541313 First trimester fetal lung explants developed dose-dependent increases in intraluminal volume in response to KGF and FGF-10. |
| GO:0090128 regulation of synapse maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from mouse Fgf7 (IDA/IMP, PMID:20505669): FGF7 from CA3 pyramidal neurons organizes inhibitory presynaptic terminals. Reason: Strong mouse genetic and rescue evidence for a target-derived synaptogenic role; a genuine but tissue-specific, non-core function in the nervous system. Supporting Evidence: PMID:20505669 FGF22 and FGF7, promote the organization of excitatory and inhibitory presynaptic terminals, respectively, as target-derived presynaptic organizers. PMID:20505669 These presynaptic defects are rescued by postsynaptic expression of the appropriate FGF. |
| GO:0098794 postsynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse FGF7 localizes to dendrites of CA3 pyramidal neurons at inhibitory (gephyrin-positive) postsynaptic sites. Reason: Supported by mouse localization data; relevant to the non-core synaptogenic role. Supporting Evidence: PMID:20505669 in hippocampal neurons, FGF22 and FGF7 are specifically localized at glutamatergic and GABAergic synapses, respectively |
| GO:0098982 GABA-ergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse FGF7 is specifically localized at GABAergic synapses in hippocampal neurons. Reason: Supported by mouse localization and loss-of-function data; non-core neural context. Supporting Evidence: PMID:20505669 in hippocampal neurons, FGF22 and FGF7 are specifically localized at glutamatergic and GABAergic synapses, respectively |
| GO:0008201 heparin binding | IDA PMID:2915979 Purification and characterization of a newly identified grow... | NEW | Summary: Native KGF/FGF7 was purified from fibroblast conditioned medium by heparin-Sepharose affinity chromatography, showing direct heparin binding; heparan sulfate acts as the coreceptor that stabilizes FGF-FGFR complexes. Reason: Heparin binding is an activity of FGF7 itself (not a downstream effect) and is required for productive FGFR2b signalling complexes. It is annotated to rat/mouse FGF7 by ISO but absent from human GOA. Comparator paracrine FGFs (FGF1, FGF2, FGF10) carry heparin binding. Supporting Evidence: PMID:2915979 was purified to homogeneity by a combination of ultrafiltration, heparin-Sepharose affinity chromatography, and hydrophobic chromatography on a C4 reversed-phase HPLC column. file:human/FGF7/FGF7-uniprot.txt Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. |
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Download this section (compressed HTML)Q: PMID:11023837 (checked in full text) contains no FGF7 data, so which publication was intended for the UniProt IDA of FGF7 in mesenchymal cell proliferation (GO:0010463)?
Q: Which FGF7 functions in human epithelia are non-redundant with FGF10 and FGF22, given the mild phenotype of Fgf7-null mice?
Q: Is the synaptogenic role of FGF7 at inhibitory hippocampal synapses conserved in human brain, and which receptor isoform mediates it presynaptically?
Q: Should the GO FGF-family PAINT node for cytoplasm (PTN000160075) be restricted so it does not propagate to classically secreted, signal-peptide-bearing FGFs such as FGF7?
Experiment: Measure FGF7 binding kinetics and signalling (pFRS2, pERK) across FGFR1-4 IIIb/IIIc isoforms with defined heparan sulfate oligosaccharides and FGFBP1, in isogenic cell backgrounds.
Hypothesis: FGF7 selectivity for FGFR2b is absolute at physiological concentrations and is tuned by heparan sulfate structure and FGFBP1.
Type: biochemistry/quantitative signaling
Experiment: Knock out FGF7 in human stromal fibroblasts co-cultured with keratinocyte or airway epithelial organoids, with and without FGF10 knockout, and quantify epithelial proliferation, migration and barrier repair after injury.
Hypothesis: Stromal FGF7 is required for maximal epithelial repair responses but is partially compensated by FGF10.
Type: genome editing/organoid co-culture
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