Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:P21802-1 FGFR2
| Class:Id | ReferenceIsoform:54816 |
|---|---|
| _chainChangeLog | signal peptide:1-21 added on Sat February 7 2015;chain:22-821 added on Sat February 7 2015 |
| _displayName | UniProt:P21802-1 FGFR2 |
| _timestamp | 2025-02-21 19:06:39 |
| chain | signal peptide:1-21 chain:22-821 |
| checksum | 6CD5001C960ED82F |
| 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, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.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 ARQ 523 and ARQ 069; these compounds maintain the kinase in an inactive conformation and inhibit autophosphorylation.SUBUNIT Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in vitro). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Isoform 1 has high affinity for FGF1 and FGF2, but low affinity for FGF7. Isoform 3 has high affinity for FGF1 and FGF7, and has much higher affinity for FGF7 than isoform 1 (in vitro). 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 PLCG1, GRB2 and PAK4. Interacts with FLRT2 (By similarity).INTERACTION Detected on osteoblast plasma membrane lipid rafts. After ligand binding, the activated receptor is rapidly internalized and degraded.SUBCELLULAR LOCATION After ligand binding, the activated receptor is rapidly internalized and degraded.SUBCELLULAR LOCATION After ligand binding, the activated receptor is rapidly internalized and degraded.SUBCELLULAR LOCATION The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Alternative splicing events affecting the third Ig-like domain are crucial for ligand selectivity.PTM Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on several tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer. Phosphorylation at Tyr-769 is essential for interaction with PLCG1.PTM N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.PTM Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome.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 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.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.SEQUENCE CAUTION Contaminating sequence. Somatic variant that appeared in a cancer cell line as a result of genome instability.SEQUENCE CAUTION Contaminating sequence. Somatic variant that appeared in a cancer cell line as a result of genome instability.SEQUENCE CAUTION Contaminating sequence. Somatic variant that appeared in a cancer cell line as a result of genome instability.SEQUENCE CAUTION Contaminating sequence. Somatic variant that appeared in a cancer cell line as a result of genome instability.SEQUENCE CAUTION Contaminating sequence. Somatic variant that appeared in a cancer cell line as a result of genome instability.SEQUENCE CAUTION Contaminating sequence. Somatic variant that appeared in a cancer cell line as a result of genome instability.SEQUENCE CAUTION Extended N-terminus. |
| description | recommendedName: Fibroblast growth factor receptor 2 shortName: FGFR-2 ecNumber evidence="31 37 42 43"2.7.10.1 alternativeName: K-sam shortName: KGFR alternativeName: Keratinocyte growth factor receptor cdAntigenNameCD332/cdAntigenName |
| geneName | FGFR2 BEK KGFR KSAM |
| identifier | P21802 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Apoptosis ATP-binding Cell membrane Craniosynostosis Cytoplasmic vesicle Disease variant Disulfide bond Ectodermal dysplasia Glycoprotein Golgi apparatus Heparin-binding Immunoglobulin domain Intellectual disability Kinase Lacrimo-auriculo-dento-digital syndrome Membrane Nucleotide-binding Phosphoprotein Proteomics identification Proto-oncogene 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 | FGFR2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:2023822] ENSEMBL:ENSG00000066468 FGFR2 [Homo sapiens] |
| secondaryIdentifier | FGFR2_HUMAN B4DFC2 E7EVR6 E9PCR0 P18443 Q01742 Q12922 Q14300 Q14301 Q14302 Q14303 Q14304 Q14305 Q14672 Q14718 Q14719 Q1KHY5 Q86YI4 Q8IXC7 Q96KL9 Q96KM0 Q96KM1 Q96KM2 Q9NZU2 Q9NZU3 Q9UD01 Q9UD02 Q9UIH3 Q9UIH4 Q9UIH5 Q9UIH6 Q9UIH7 Q9UIH8 Q9UM87 Q9UMC6 Q9UNS7 Q9UQH7 Q9UQH8 Q9UQH9 Q9UQI0 |
| sequenceLength | 821 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P21802-1 |
| (referenceEntity) | [EntityWithAccessionedSequence:189920] FGFR2c long [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:190416] p-8Y-FGFR2c long [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1637888] FGFR2c A314D [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1637889] FGFR2c A315T [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1637916] FGFR2c P253R [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2011852] FGFR2c S252W [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2011879] p-8Y-FGFR2c S252W [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2011880] p-8Y-FGFR2c P253R [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2029861] p-8Y-FGFR2c Y375C [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2029862] p-8Y-FGFR2c W290G [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:190414] O4'-phospho-L-tyrosine at unknown position [ModifiedResidue:1307864] O4'-phospho-L-tyrosine at 466 [ModifiedResidue:1307872] O4'-phospho-L-tyrosine at 586 [ModifiedResidue:1307873] O4'-phospho-L-tyrosine at 588 [ModifiedResidue:1307882] O4'-phospho-L-tyrosine at 656 [ModifiedResidue:1307883] O4'-phospho-L-tyrosine at 657 [ModifiedResidue:1307889] O4'-phospho-L-tyrosine at 733 [ModifiedResidue:1307900] O4'-phospho-L-tyrosine at 769 [ModifiedResidue:1307907] O4'-phospho-L-tyrosine at 779 [ReplacedResidue:2029818] L-serine 372 replaced with L-cysteine |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:P21802-1 FGFR2 (54816)
