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Details on Person UniProt:P22607-1 FGFR3
| Class:Id | ReferenceIsoform:54818 |
|---|---|
| _chainChangeLog | signal peptide:1-22 added on Sat February 7 2015;chain:23-806 added on Sat February 7 2015 |
| _displayName | UniProt:P22607-1 FGFR3 |
| _timestamp | 2025-02-21 19:06:43 |
| chain | signal peptide:1-22 chain:23-806 |
| checksum | BC5EA75EA46F447E |
| comment | FUNCTION Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling.CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)ACTIVITY REGULATION Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by SU5402.SUBUNIT Monomer. Homodimer after ligand binding. Interacts with FGF1, FGF2, FGF4, FGF6; FGF8, FGF9, FGF10, FGF17, FGF18, FGF19, FGF20 and FGF23 (in vitro). Interacts with KLB. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19 and FGF21. Interacts with PIK3R1, PLCG1, SOCS1 and SOCS3. Isoform 3 forms disulfide-linked dimers.INTERACTION The activated receptor is rapidly internalized and degraded. Detected in intracellular vesicles after internalization of the autophosphorylated receptor.SUBCELLULAR LOCATION Expressed in brain, kidney and testis. Very low or no expression in spleen, heart, and muscle. In 20- to 22-week old fetuses it is expressed at high level in kidney, lung, small intestine and brain, and to a lower degree in spleen, liver, and muscle. Isoform 2 is detected in epithelial cells. Isoform 1 is not detected in epithelial cells. Isoform 1 and isoform 2 are detected in fibroblastic cells.DOMAIN The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans.PTM Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer. Phosphorylation at Tyr-724 is essential for stimulation of cell proliferation and activation of PIK3R1, STAT1 and MAP kinase signaling. Phosphorylation at Tyr-760 is required for interaction with PIK3R1 and PLCG1.PTM Ubiquitinated. Is rapidly ubiquitinated after ligand binding and autophosphorylation, leading to receptor internalization and degradation. Subject to both proteasomal and lysosomal degradation.PTM N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry. Somatic mutations can constitutively activate FGFR3.DISEASE The gene represented in this entry is involved in disease pathogenesis.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving FGFR3 is found in multiple myeloma. Translocation t(4;14)(p16.3;q32.3) with the IgH locus.DISEASE The disease may be caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The gene represented in this entry may be involved in disease pathogenesis.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.SEQUENCE CAUTION Extended N-terminus. |
| description | recommendedName: Fibroblast growth factor receptor 3 shortName: FGFR-3 ecNumber: 2.7.10.1 cdAntigenNameCD333/cdAntigenName |
| geneName | FGFR3 JTK4 |
| identifier | P22607 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Apoptosis ATP-binding Cell membrane Chromosomal rearrangement Craniosynostosis Cytoplasmic vesicle Deafness Disease variant Disulfide bond Dwarfism Ectodermal dysplasia Endoplasmic reticulum Glycoprotein Immunoglobulin domain Kinase Lacrimo-auriculo-dento-digital syndrome Membrane Nucleotide-binding Phosphoprotein Proteomics identification Receptor Reference proteome Repeat Secreted Signal Transferase Transmembrane Transmembrane helix Tyrosine-protein kinase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | FGFR3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8990121] ENSEMBL:ENSG00000068078 FGFR3 [Homo sapiens] |
| secondaryIdentifier | FGFR3_HUMAN D3DVP9 D3DVQ0 Q14308 Q16294 Q16608 Q59FL9 |
| sequenceLength | 806 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P22607-1 |
| (referenceEntity) | [EntityWithAccessionedSequence:189913] FGFR3c [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:190382] p-6Y-FGFR3c [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2011857] FGFR3c P250R [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2011870] p6Y-FGFR3c P250R [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:190383] O4'-phospho-L-tyrosine at unknown position [ModifiedResidue:1307866] O4'-phospho-L-tyrosine at 648 [ModifiedResidue:1307875] O4'-phospho-L-tyrosine at 647 [ModifiedResidue:1307886] O4'-phospho-L-tyrosine at 724 [ModifiedResidue:1307891] O4'-phospho-L-tyrosine at 760 [ModifiedResidue:1307897] O4'-phospho-L-tyrosine at 770 [ModifiedResidue:1307975] O4'-phospho-L-tyrosine at 577 [ReplacedResidue:2011856] L-proline 250 replaced with L-arginine |
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No pathways have been reviewed or authored by UniProt:P22607-1 FGFR3 (54818)
