Fibroblast growth factor 23 (FGF23) is a secreted endocrine member of the FGF19 subfamily of fibroblast growth factors, produced mainly by osteocytes and osteoblasts, that acts as the principal phosphaturic hormone. Circulating intact FGF23 binds FGFR1c (and to a lesser extent FGFR3c/FGFR4) in a 1:1:1 complex with the transmembrane co-receptor alpha-Klotho, which tethers the FGF23 C-terminal tail and confers high-affinity binding; receptor dimerisation additionally requires heparan sulfate. In the renal proximal tubule, FGF23-Klotho-FGFR signalling via FRS2/ERK reduces NaPi-2a/2c sodium-phosphate cotransporters, promoting phosphate excretion, and suppresses CYP27B1 while inducing CYP24A1, lowering 1,25-dihydroxyvitamin D. In the parathyroid it suppresses PTH synthesis and secretion. FGF23 production is stimulated by phosphate and calcitriol. Activity is controlled post-translationally: furin-type proprotein convertase cleavage at the R176XXR179 site inactivates the hormone (the released C-terminal peptide can antagonise intact FGF23), GALNT3 O-glycosylation at Thr178 protects the site, and FAM20C phosphorylation of Ser180 opposes this glycosylation. Cleavage-resistant missense mutations cause autosomal dominant hypophosphatemic rickets, and loss-of-function mutations cause hyperphosphatemic familial tumoral calcinosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005104 fibroblast growth factor receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: FGF23 binds FGF receptors; its physiological receptor is FGFR1c converted into a high-affinity FGF23 receptor by the co-receptor alpha-Klotho. Electronic orthology transfer from mouse Fgf23. Reason: Receptor binding is the core molecular function of FGF23 as a ligand. Direct binding to FGFR1c in a ternary complex with Klotho has been demonstrated biochemically and structurally, so this IEA is correct (the more specific GO:0005105 is also present). Supporting Evidence: PMID:17086194 Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. PMID:19966287 the soluble ectodomains of FGFR1c and Klotho are sufficient to form a ternary complex with FGF23 in vitro PMID:29342138 tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability |
| GO:0005105 type 1 fibroblast growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: FGF23 binds FGFR1 (the IIIc isoform), its principal signalling receptor in kidney and parathyroid, in a complex with alpha-Klotho. PAINT IBD placement within the FGF ligand family. Reason: FGFR1c is the main receptor for FGF23: Klotho converts FGFR1(IIIc) into the FGF23 receptor and the crystal structure of the 1:1:1 FGF23-FGFR1c-alpha-Klotho complex shows direct FGF23-FGFR1c contact. FGF23 lies in the clade that inherited receptor binding, and there is target-specific experimental support, so the IBA is sound and at an appropriate level of specificity. Supporting Evidence: PMID:17086194 Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. PMID:29342138 tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability PMID:19966287 the soluble ectodomains of FGFR1c and Klotho are sufficient to form a ternary complex with FGF23 in vitro |
| GO:0005105 type 1 fibroblast growth factor receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic orthology transfer (mouse Fgf23) of FGFR1 binding. Reason: Consistent with direct experimental and structural evidence for FGF23 binding to FGFR1c in the Klotho ternary complex. Supporting Evidence: PMID:17086194 Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. PMID:29342138 tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability |
| GO:0005515 protein binding | IPI PMID:17086194 Klotho converts canonical FGF receptor into a specific recep... | MODIFY | Summary: IPI for binding to mouse Klotho (O35082). Urakawa et al. showed that Klotho binds FGF23 and, together with FGFR1(IIIc), reconstitutes the FGF23 receptor. Reason: Generic 'protein binding' is uninformative. The interaction reported is the ligand engaging its Klotho-FGFR1c receptor complex; the informative molecular function is fibroblast growth factor receptor binding (the Klotho-FGFR1c complex is the FGF23 receptor). The interaction itself is real and well established. Proposed replacements: fibroblast growth factor receptor binding Supporting Evidence: PMID:17086194 Using a renal homogenate, we found that Klotho binds to FGF23. PMID:17086194 Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. |
| GO:0005515 protein binding | IPI PMID:19966287 Isolated C-terminal tail of FGF23 alleviates hypophosphatemi... | MODIFY | Summary: IPI for binding to mouse Klotho (O35082); Goetz et al. show that the FGF23 C-terminal tail binds a composite site at the FGFR1c-Klotho interface. Reason: Generic 'protein binding' is uninformative. The measured interaction is FGF23 binding the binary FGFR1c-Klotho receptor complex, best captured as fibroblast growth factor receptor binding. Proposed replacements: fibroblast growth factor receptor binding Supporting Evidence: PMID:19966287 the soluble ectodomains of FGFR1c and Klotho are sufficient to form a ternary complex with FGF23 in vitro |
| GO:0005515 protein binding | IPI PMID:19966287 Isolated C-terminal tail of FGF23 alleviates hypophosphatemi... | MODIFY | Summary: IPI for binding to human FGFR1 (P11362); the FGFR1c ectodomain with Klotho forms a ternary complex with FGF23. Reason: Generic 'protein binding' is uninformative; the partner is FGFR1 so the specific informative term is type 1 fibroblast growth factor receptor binding (already present as IBA/IEA). Proposed replacements: type 1 fibroblast growth factor receptor binding Supporting Evidence: PMID:19966287 the soluble ectodomains of FGFR1c and Klotho are sufficient to form a ternary complex with FGF23 in vitro PMID:29342138 tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: IPI for SMAD4 (Q13485) from a high-throughput screen for mutation-directed neo-protein-protein interactions in cancer. Reason: Generic 'protein binding' is uninformative and no specific molecular function can be derived from this screen-level interaction between a secreted hormone and a nuclear/cytoplasmic transcriptional co-regulator that do not share a compartment in vivo. Removal of the GO annotation does not assert that the reported assay result is false. Supporting Evidence: file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: FGF23 is a secreted endocrine hormone that acts extracellularly on Klotho-FGFR complexes. PAINT IBD for the secreted FGF family. Reason: FGF23 has a cleavable signal peptide, secretion requires GALNT3-mediated O-glycosylation, and the protein circulates to act on kidney and parathyroid. Active-in extracellular region is correct. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions |
| GO:0005576 extracellular region | IDA PMID:16638743 Polypeptide GalNAc-transferase T3 and familial tumoral calci... | ACCEPT | Summary: Kato et al. showed FGF23 is secreted and that secretion requires GALNT3-directed O-glycosylation. Reason: Direct experimental evidence for secretion; the extracellular region is where FGF23 functions. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. file:human/FGF23/FGF23-deep-research-falcon.md FGF23 is produced primarily by osteocytes and osteoblast-lineage cells within bone tissue, which serve as the main endocrine source |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt subcellular-location mapping (Secreted). Reason: Consistent with experimental evidence of secretion. Supporting Evidence: file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-109699 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1839094 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1839098 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1839100 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190256 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190258 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190261 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190265 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190268 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190326 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190388 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190413 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-190429 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-191062 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2012073 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2012074 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2023451 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2023455 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2033472 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2033486 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2077420 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2077424 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2316434 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2400009 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654147 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654148 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654149 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654151 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654157 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654159 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654163 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654165 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654167 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654169 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654222 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654224 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654392 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654397 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654399 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654402 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654404 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654406 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654407 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654408 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654409 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654413 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654416 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654418 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654422 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654423 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654425 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654426 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654428 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654560 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654562 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654565 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654566 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654569 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654571 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654573 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654575 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654578 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654582 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654584 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654586 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654587 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654591 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654592 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654594 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654596 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654597 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654600 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654603 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654605 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654607 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654608 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654612 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654614 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654615 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654618 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654620 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654622 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654623 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654625 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654628 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654631 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654633 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654634 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654637 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654640 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654641 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654643 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654646 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654647 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654651 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654653 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654655 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654658 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654659 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654662 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654663 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654664 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654667 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654669 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654672 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654673 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654677 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654679 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654684 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654690 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654692 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654697 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654701 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654705 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654709 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654714 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654717 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654729 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654730 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654734 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5654748 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655233 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655240 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655241 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655243 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655244 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655245 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655247 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655262 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655263 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655266 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655268 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655269 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655270 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655277 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655278 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655285 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655289 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655290 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655295 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655301 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655315 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655320 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655323 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655326 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655339 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5655343 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5656064 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8851632 | ACCEPT | Summary: Reactome places FGF23 in the extracellular region as a ligand in FGFR signalling reactions (ligand-receptor binding and downstream RTK signalling events). Reason: FGF23 is a secreted hormone that binds FGFR-Klotho complexes at the cell surface; extracellular localisation of the ligand in these reactions is correct. Downstream intracellular Reactome events (e.g. PI3K, RAS, PLCG1) list FGF23 only as the extracellular ligand of the activated receptor complex. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | REMOVE | Summary: IBA 'is_active_in cytoplasm' propagated from the FGF family node (seeded by FGF1/FGF2-type and intracellular FGF members). Reason: FGF23 has an N-terminal signal peptide (residues 1-24) and is a classically secreted endocrine hormone; its activity (receptor binding) occurs extracellularly. The cytoplasmic activity inferred at the family node derives from members that lack signal peptides (FGF1/FGF2) or are intracellular (FGF11-14). FGF23 is inside the secreted endocrine subfamily that lost this property; its only intracellular presence is transit through the ER/Golgi secretory pathway, which does not constitute being active in the cytoplasm. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000160075 · PTN000160075 SUPPORTS SOURCE BUT NOT TARGET Family-level node for the FGF ligand family; cytoplasmic activity at this node reflects members without signal peptides (FGF1/FGF2-type) and intracellular FGFs, not the secreted endocrine subfamily. UniProtKB:P05230 · FGF1 SUPPORTS SOURCE BUT NOT TARGET FGF1 lacks a classical signal peptide and has documented intracellular/nuclear pools; FGF23 has a cleaved signal peptide (residues 1-24) and is classically secreted. Supporting Evidence: file:human/FGF23/FGF23-uniprot.txt SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}. PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | KEEP AS NON CORE | Summary: Reactome FAM20C substrate phosphorylation reaction places FGF23 in the ER lumen during secretory processing. Reason: FGF23 transits the ER/Golgi lumen, where it is phosphorylated by FAM20C and O-glycosylated by GALNT3 before secretion; this is a transient biosynthetic location and not where FGF23 functions. Supporting Evidence: PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-8851619 | KEEP AS NON CORE | Summary: Reactome GALNT3 O-glycosylation reactions place FGF23 in the Golgi lumen. Reason: GALNT3 O-glycosylates FGF23 at Thr178 in the Golgi, protecting it from furin-type cleavage and permitting secretion of intact hormone. The Golgi lumen is a genuine but transient processing location, not the site of FGF23 function. Supporting Evidence: Reactome:R-HSA-8851619 Glycosylation is necessary for FGF23 secretion from the cell and that is mediated by polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-8851632 | KEEP AS NON CORE | Summary: Reactome GALNT3 O-glycosylation reactions place FGF23 in the Golgi lumen. Reason: GALNT3 O-glycosylates FGF23 at Thr178 in the Golgi, protecting it from furin-type cleavage and permitting secretion of intact hormone. The Golgi lumen is a genuine but transient processing location, not the site of FGF23 function. Supporting Evidence: Reactome:R-HSA-8851619 Glycosylation is necessary for FGF23 secretion from the cell and that is mediated by polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) PMID:16638743 we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation |
| GO:0008083 growth factor activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Growth factor activity propagated across the FGF ligand family. Reason: FGF23 is a member of the FGF family and can activate FGFRs, and 'growth factor activity' is the family-level ligand activity. However FGF23 physiologically acts as an endocrine hormone that regulates phosphate and vitamin D metabolism rather than as a mitogen; overexpression in osteoblast cultures did not affect progenitor proliferation. The more informative activity is hormone activity (proposed as NEW). Supporting Evidence: PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions PMID:18282132 Nodule formation and mineralization, but not osteoprogenitor proliferation, were independently suppressed by overexpression of FGF23 in RC cells. |
| GO:0008083 growth factor activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO mapping from the FGF family domain (IPR002209). Reason: Family-level mapping; correct for the FGF fold but FGF23's physiological role is as a hormone (see NEW hormone activity). Supporting Evidence: file:human/FGF23/FGF23-uniprot.txt Belongs to the heparin-binding growth factors family. PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions |
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell proliferation propagated from paracrine mitogenic FGFs. Reason: Mitogenic activity is characteristic of paracrine FGFs; FGF23's physiological actions are phosphaturic and vitamin D/PTH regulatory. In osteoblast cultures FGF23 overexpression did not alter osteoprogenitor proliferation. Not a demonstrated physiological function of FGF23. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE ROLE CONFLATION Sources checked: PANTHER:PTN000160075 · PTN000160075 SUPPORTS SOURCE BUT NOT TARGET Mitogenic activity for cultured fibroblasts is the paracrine-FGF phenotype behind this node; FGF23 overexpression did not alter osteoprogenitor proliferation. Supporting Evidence: PMID:18282132 Nodule formation and mineralization, but not osteoprogenitor proliferation, were independently suppressed by overexpression of FGF23 in RC cells. PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: FGF23 is the ligand that initiates FGFR signalling through the Klotho-FGFR1c complex. Reason: As the activating ligand, FGF23 directly participates in the FGFR signalling pathway; Klotho enhances FGF23-induced FRS2 and ERK phosphorylation and FGF23 activates MAPK in parathyroid. Supporting Evidence: PMID:16436388 Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. PMID:17992255 FGF23 activated the MAPK pathway in the parathyroid through ERK1/2 phosphorylation and increased early growth response 1 mRNA levels PMID:17086194 Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. |
| GO:0010966 regulation of phosphate transport | IDA PMID:11409890 FGF-23 inhibits renal tubular phosphate transport and is a P... | MODIFY | Summary: Bowe et al. showed that FGF23 (wild-type and ADHR R179Q) inhibits phosphate uptake in renal epithelial cells. Reason: The direction and the transport system are both established: FGF23 inhibits phosphate uptake in renal epithelial cells and reduces renal NaPi-2a (SLC34A1) mRNA and protein, so the non-directional parent term understates what the evidence shows. Replace with negative regulation of sodium-dependent phosphate transport. Proposed replacements: negative regulation of sodium-dependent phosphate transport Supporting Evidence: PMID:11409890 both wild-type FGF-23 and the ADHR mutant, FGF-23(R179Q), inhibit phosphate uptake in renal epithelial cells PMID:15040831 accompanied with a reduction in renal mRNA and protein levels for the type IIa sodium-phosphate cotransporter (NaPi-2a) |
| GO:0022008 neurogenesis | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Neurogenesis propagated from developmental paracrine FGFs. Reason: No evidence that FGF23 functions in neurogenesis; FGF23 is a bone-derived endocrine regulator of mineral metabolism. The family-level node placement reflects paracrine FGFs (e.g. FGF8, FGF2) whose developmental roles are not shared by the endocrine subfamily. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000160075 · PTN000160075 SUPPORTS SOURCE BUT NOT TARGET Developmental neurogenesis at this node derives from paracrine FGFs (e.g. FGF8, FGF2, FGF10); the endocrine FGF19/21/23 subfamily acts on metabolic target organs. Supporting Evidence: PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions |
| GO:0030334 regulation of cell migration | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Regulation of cell migration propagated from paracrine FGFs. Reason: No experimental evidence for FGF23 regulating cell migration in normal physiology; FGF23's documented functions are endocrine regulation of phosphate, vitamin D and PTH. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000160075 · PTN000160075 SUPPORTS SOURCE BUT NOT TARGET Cell-migration regulation at this node derives from paracrine FGFs acting locally on mesenchymal and epithelial cells; no such role is documented for FGF23. Supporting Evidence: PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions |
| GO:0030502 negative regulation of bone mineralization | IDA PMID:18282132 Overexpression of fibroblast growth factor 23 suppresses ost... | KEEP AS NON CORE | Summary: Wang et al. overexpressed human FGF23 in rat calvaria cell cultures and found suppression of matrix mineralization, abrogated by an FGFR inhibitor. Reason: Supported by an in vitro overexpression study; a local, FGFR-dependent effect on bone mineralization is plausible, but FGF23's primary role is systemic (renal) regulation of phosphate. Keep as non-core. Supporting Evidence: PMID:18282132 FGF23 overexpression suppresses not only osteoblast differentiation but also matrix mineralization independently of its systemic effects on Pi homeostasis |
| GO:0032026 response to magnesium ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat Fgf23 of 'response to magnesium ion', reflecting regulation of Fgf23 expression by magnesium. Reason: This describes a change in FGF23 expression/levels, i.e. FGF23 as a regulated target, not an activity of the FGF23 protein. Not supported by human experimental evidence and not informative about FGF23 function. Supporting Evidence: PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions |
| GO:0042359 vitamin D metabolic process | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl orthology transfer of 'vitamin D metabolic process' from rat. Reason: FGF23 does not catalyse vitamin D metabolism; it regulates it by suppressing renal CYP27B1 (1alpha-hydroxylase) and inducing CYP24A1 (24-hydroxylase) via FGFR-Klotho signalling. The appropriate term is a regulation term. Proposed replacements: negative regulation of vitamin D biosynthetic process Supporting Evidence: PMID:15040831 FGF-23 reduced renal mRNA for 25-hydroxyvitamin D-1alpha-hydroxylase and increased that for 25-hydroxyvitamin D-24-hydroxylase starting at 1 h PMID:14966565 indicating that FGF23 is essential for normal phosphate and vitamin D metabolism |
| GO:0042369 vitamin D catabolic process | IDA PMID:15040831 FGF-23 is a potent regulator of vitamin D metabolism and pho... | MODIFY | Summary: Shimada et al. 2004: FGF23 injection increased renal 24-hydroxylase (CYP24A1) mRNA and reduced 1alpha-hydroxylase mRNA, lowering serum 1,25(OH)2D. Reason: The catabolic step (24-hydroxylation) is catalysed by CYP24A1, whose expression FGF23 signalling induces; FGF23 itself performs no step of vitamin D catabolism. The evidence supports FGF23 as a regulator of vitamin D metabolism. GO has no 'regulation of vitamin D catabolic process' term, so the best available replacement is negative regulation of vitamin D biosynthetic process (reduced 1alpha-hydroxylase, the dominant effect on 1,25(OH)2D). A new term for positive regulation of vitamin D catabolism is raised in suggested_questions. Proposed replacements: negative regulation of vitamin D biosynthetic process Supporting Evidence: PMID:15040831 FGF-23 reduced renal mRNA for 25-hydroxyvitamin D-1alpha-hydroxylase and increased that for 25-hydroxyvitamin D-24-hydroxylase starting at 1 h |
| GO:0043410 positive regulation of MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: Positive regulation of MAPK cascade propagated in the FGF family. Reason: FGF23 activates ERK1/2 MAPK signalling through Klotho-FGFR complexes in cultured cells and in the parathyroid, and this MAPK activation mediates suppression of PTH secretion. The IBA is supported by FGF23-specific evidence. Supporting Evidence: PMID:16436388 Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. PMID:17992255 FGF23 activated the MAPK pathway in the parathyroid through ERK1/2 phosphorylation and increased early growth response 1 mRNA levels |
| GO:0044320 cellular response to leptin stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of 'cellular response to leptin stimulus', reflecting induction of Fgf23 expression by leptin. Reason: Describes regulation of FGF23 expression (FGF23 as a response readout), not an activity of the FGF23 protein; not informative about FGF23 function. Supporting Evidence: PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions |
| GO:0045668 negative regulation of osteoblast differentiation | IDA PMID:18282132 Overexpression of fibroblast growth factor 23 suppresses ost... | KEEP AS NON CORE | Summary: Wang et al. 2008: FGF23 overexpression suppressed osteoblast differentiation (nodule formation) in rat calvaria cell cultures. Reason: In vitro overexpression evidence for a local effect on osteoblast differentiation; secondary to FGF23's primary endocrine role. Supporting Evidence: PMID:18282132 FGF23 overexpression suppresses not only osteoblast differentiation but also matrix mineralization independently of its systemic effects on Pi homeostasis |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from mouse of positive regulation of transcription, presumably from induction of Egr1 by FGF23-Klotho signalling. Reason: Induction of immediate-early genes such as EGR1 is a generic downstream consequence of FGFR-MAPK signalling rather than a specific function of the ligand. The informative process is FGFR signalling (GO:0008543), already annotated. Supporting Evidence: PMID:17992255 FGF23 activated the MAPK pathway in the parathyroid through ERK1/2 phosphorylation and increased early growth response 1 mRNA levels |
| GO:0046888 negative regulation of hormone secretion | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl orthology transfer from rat of negative regulation of hormone secretion (suppression of PTH secretion). Reason: FGF23 acts directly on the parathyroid via Klotho-FGFR and MAPK to decrease PTH secretion. The specific hormone is known, so the more precise term negative regulation of parathyroid hormone secretion is preferable. Proposed replacements: negative regulation of parathyroid hormone secretion Supporting Evidence: PMID:17992255 FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH |
| GO:0046888 negative regulation of hormone secretion | ISS GO_REF:0000024 | MODIFY | Summary: ISS from rat Fgf23 (Q8VI82) based on the direct parathyroid action of FGF23. Reason: Supported by rat in vivo and in vitro parathyroid studies showing FGF23 suppresses PTH secretion via MAPK. The more specific term negative regulation of parathyroid hormone secretion is preferable. Proposed replacements: negative regulation of parathyroid hormone secretion Supporting Evidence: PMID:17992255 FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH |
| GO:0055062 phosphate ion homeostasis | IMP PMID:11062477 Autosomal dominant hypophosphataemic rickets is associated w... | ACCEPT | Summary: ADHR Consortium identified FGF23 missense mutations as the cause of autosomal dominant hypophosphatemic rickets, a disorder of phosphate homeostasis. Reason: Phosphate homeostasis is the core physiological process regulated by FGF23; human genetics (ADHR gain-of-function; hyperphosphatemic tumoral calcinosis loss-of-function) and Fgf23 knockout mice establish FGF23 as the principal phosphaturic hormone. As the hormone ligand, FGF23 directly contributes to this homeostatic process. Supporting Evidence: PMID:11062477 We identified missense mutations in a gene encoding a new member of the fibroblast growth factor (FGF) family, FGF23. PMID:14966565 displayed significantly high serum phosphate with increased renal phosphate reabsorption PMID:11409890 both wild-type FGF-23 and the ADHR mutant, FGF-23(R179Q), inhibit phosphate uptake in renal epithelial cells file:human/FGF23/FGF23-deep-research-falcon.md The kidney represents the principal endocrine target organ where FGF23 exerts its canonical effects on mineral metabolism |
| GO:0055074 calcium ion homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl orthology transfer from mouse of calcium ion homeostasis. Reason: FGF23 influences calcium balance indirectly through suppression of 1,25(OH)2D and PTH and via distal tubular calcium reabsorption; this is a secondary consequence of its primary phosphate/vitamin D regulatory role. Supporting Evidence: PMID:17992255 FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH PMID:15040831 FGF-23 reduced renal mRNA for 25-hydroxyvitamin D-1alpha-hydroxylase and increased that for 25-hydroxyvitamin D-24-hydroxylase starting at 1 h |
| GO:0070371 ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl orthology transfer of ERK1 and ERK2 cascade. Reason: FGF23 triggers ERK1/2 phosphorylation through Klotho-FGFR1c; as the ligand it initiates rather than executes the cascade, so the regulation term (GO:0070374) and FGFR signalling (GO:0008543) are more apt. Retained as non-core. Supporting Evidence: PMID:16436388 Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. PMID:17992255 FGF23 activated the MAPK pathway in the parathyroid through ERK1/2 phosphorylation and increased early growth response 1 mRNA levels |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl orthology transfer of positive regulation of ERK1 and ERK2 cascade. Reason: Supported directly for FGF23: Klotho-dependent ERK phosphorylation in cultured cells and ERK1/2 phosphorylation in rat parathyroid. Supporting Evidence: PMID:16436388 Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. PMID:17992255 FGF23 activated the MAPK pathway in the parathyroid through ERK1/2 phosphorylation and increased early growth response 1 mRNA levels |
| GO:0071305 cellular response to vitamin D | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl orthology transfer from rat of cellular response to vitamin D, reflecting induction of FGF23 by 1,25(OH)2D. Reason: Calcitriol induces FGF23 production in bone, forming the endocrine feedback loop in which FGF23 then suppresses vitamin D activation. This reflects regulation of FGF23 expression rather than an activity of FGF23 itself, but it is a physiologically important and well-documented feedback. Kept as non-core. Supporting Evidence: PMID:15040831 an injection of calcitriol into normal mice increased the serum FGF-23 level within 4 h |
| GO:0071354 cellular response to interleukin-6 | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of cellular response to interleukin-6 (inflammatory induction of Fgf23 expression). Reason: Describes regulation of FGF23 expression by inflammatory cytokines, not an activity of the FGF23 protein; not informative about FGF23 function. Supporting Evidence: PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions |
| GO:0071374 cellular response to parathyroid hormone stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of cellular response to parathyroid hormone stimulus (PTH induction of Fgf23). Reason: Reflects regulation of FGF23 expression by PTH, i.e. FGF23 as a regulated target; not an activity of FGF23. FGF23's documented relation to PTH is the reverse (suppression of PTH secretion), captured by GO:2000829. Supporting Evidence: PMID:17992255 FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH |
| GO:1904383 response to sodium phosphate | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic annotation of response to sodium phosphate, reflecting induction of FGF23 by dietary/serum phosphate. Reason: High phosphate increases FGF23 secretion from osteocytes, the input arm of the phosphate-FGF23 feedback loop. This is regulation of FGF23 production rather than an FGF23 activity, but it is physiologically central; kept as non-core. Supporting Evidence: PMID:17992255 in response to high serum phosphate levels |
| GO:0005179 hormone activity | IDA PMID:17086194 Klotho converts canonical FGF receptor into a specific recep... | NEW | Summary: FGF23 is a bone-derived circulating hormone acting on kidney and parathyroid through Klotho-FGFR1c. Reason: FGF23 is produced by osteocytes/osteoblasts and acts at distant target organs (kidney, parathyroid) to regulate phosphate, vitamin D and PTH, precisely the definition of hormone activity. Recombinant FGF23 injection reproduces the endocrine effects and knockout mice lose them. This molecular-function term is more informative than the inherited growth factor activity. Not a process term, so the participation test concerns the gene's own activity: FGF23 itself is the signalling hormone. Supporting Evidence: PMID:17086194 FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions PMID:17992255 FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH PMID:14966565 indicating that FGF23 is essential for normal phosphate and vitamin D metabolism |
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Download this section (compressed HTML)Q: GO lacks a term for positive regulation of vitamin D catabolic process; should one be requested so that FGF23 (and PTH/calcitriol-responsive regulators) can capture the CYP24A1-inducing arm of vitamin D regulation distinctly from suppression of CYP27B1?
Q: Does the C-terminal FGF23 fragment released by furin cleavage act as a physiological endogenous antagonist of intact FGF23 at the Klotho-FGFR1c complex, and should it be represented separately (e.g. as a chain-level annotation)?
Q: Are the Klotho-independent actions of high FGF23 (e.g. FGFR4-mediated cardiomyocyte hypertrophy, reported in chronic kidney disease) physiological functions of FGF23 or pathological off-target effects of supraphysiological concentrations?
Q: How much do FGFR3c and FGFR4 contribute, relative to FGFR1c, to FGF23-Klotho signalling in the proximal versus distal tubule in vivo?
Experiment: Tubule-segment-specific conditional deletion of Fgfr1, Fgfr3 and Fgfr4 (singly and in combination) in mice, followed by acute recombinant FGF23 challenge with readouts of NaPi-2a protein, Cyp27b1/Cyp24a1 transcripts, ERK phosphorylation and urinary phosphate excretion.
Hypothesis: FGF23 signalling in the proximal tubule requires FGFR1c specifically, with FGFR3c/FGFR4 dispensable.
Type: conditional genetics with acute hormone challenge
Experiment: Quantify intact FGF23 and the free C-terminal fragment separately by targeted mass spectrometry in human plasma across normal, ADHR and CKD cohorts, and test the measured fragment concentrations for competition against intact FGF23 in a Klotho-FGFR1c reporter assay.
Hypothesis: The furin-released C-terminal FGF23 peptide circulates at concentrations sufficient to antagonise intact FGF23 at the Klotho-FGFR1c complex.
Type: quantitative proteomics plus receptor-activation assay
Experiment: Compare mineralization and osteoblast differentiation markers in osteoblast cultures from Fgf23-null versus wild-type mice, with add-back of physiological concentrations of intact FGF23 with and without soluble alpha-Klotho, and with FGFR inhibition.
Hypothesis: FGF23 suppression of osteoblast mineralization is a local autocrine action rather than an artefact of overexpression.
Type: primary cell culture with genetic loss of function
Experiment: Parathyroid-specific Kl deletion in mice, followed by recombinant FGF23 infusion, measuring PTH secretion, PTH mRNA, parathyroid ERK1/2 phosphorylation and Egr1 induction.
Hypothesis: Direct parathyroid suppression by FGF23 requires alpha-Klotho in parathyroid chief cells.
Type: tissue-specific knockout with hormone infusion
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