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:P16092 Fgfr1
| Class:Id | ReferenceGeneProduct:90401 |
|---|---|
| _chainChangeLog | signal peptide:1-21 added on Sat February 7 2015;chain:22-822 added on Sat February 7 2015 |
| _displayName | UniProt:P16092 Fgfr1 |
| _timestamp | 2025-02-21 18:56:36 |
| chain | signal peptide:1-21 chain:22-822 |
| checksum | D5A4695FA680926B |
| 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 embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. 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. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation (By similarity).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 sequential autophosphorylation on tyrosine residues (By similarity).SUBUNIT Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF5, FGF6, FGF8, FGF10, FGF19, FGF21, FGF22 and FGF23 (in vitro) (PubMed:10821861, PubMed:1309590, PubMed:17086194). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19, FGF21 and FGF23. Interacts (phosphorylated on Tyr-766) with PLCG1 (via SH2 domains). Interacts with FRS2. Interacts with RPS6KA1. Interacts (via C-terminus) with NEDD4 (via WW3 domain). Interacts with KL (PubMed:17086194). Interacts with SHB (via SH2 domain) (PubMed:12181353). Interacts with GRB10 (By similarity). Interacts with ANOS1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2 (By similarity). Interacts with SOX2 and SOX3 (PubMed:17728342). Interacts with FLRT1, FLRT2 and FLRT3 (PubMed:16872596). Found in a ternary complex with FGF1 and ITGAV:ITGB3 (By similarity).INTERACTION After ligand binding, both receptor and ligand are rapidly internalized. Can translocate to the nucleus after internalization, or by translocation from the endoplasmic reticulum or Golgi apparatus to the cytosol, and from there to the nucleus.SUBCELLULAR LOCATION Widely expressed.DOMAIN The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains (By similarity).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 and proceeds in a highly ordered manner. Initial autophosphorylation at Tyr-653 increases the kinase activity by a factor of 50 to 100. After this, Tyr-583 becomes phosphorylated, followed by phosphorylation of Tyr-463, Tyr-766, Tyr-583 and Tyr-585. In a third stage, Tyr-654 is autophosphorylated, resulting in a further tenfold increase of kinase activity. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation (By similarity).PTM Ubiquitinated. FGFR1 is rapidly ubiquitinated by NEDD4 after autophosphorylation, leading to internalization and lysosomal degradation. CBL is recruited to activated FGFR1 via FRS2 and GRB2, and mediates ubiquitination and subsequent degradation of FGFR1 (By similarity).PTM N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.DISRUPTION PHENOTYPE Embryonic lethality around gastrulation, due to growth defects during early embryonic development and aberrant mesoderm patterning.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.SEQUENCE CAUTION Proposes two coding sequences for the same mRNA. |
| description | recommendedName: Fibroblast growth factor receptor 1 shortName: FGFR-1 shortName: bFGF-R-1 ecNumber evidence="2"2.7.10.1 alternativeName: Basic fibroblast growth factor receptor 1 alternativeName: MFR alternativeName: Proto-oncogene c-Fgr cdAntigenNameCD331/cdAntigenName |
| geneName | Fgfr1 Flg |
| identifier | P16092 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing ATP-binding Cell membrane Cytoplasm Cytoplasmic vesicle Disulfide bond Glycoprotein Heparin-binding Immunoglobulin domain Kinase Membrane Nucleotide-binding Nucleus Phosphoprotein Receptor Reference proteome Repeat Signal Transferase Transmembrane Transmembrane helix Tyrosine-protein kinase Ubl conjugation |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:6807888] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9627708] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | Fgfr1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | FGFR1_MOUSE E9Q2P4 Q01736 Q60830 Q61562 Q80T10 Q8CFK8 Q9QZM7 |
| sequenceLength | 822 |
| species | [Species:48892] Mus musculus |
| (isoformParent) | [ReferenceIsoform:147295] UniProt:P16092-2 Fgfr1 [Mus musculus] [ReferenceIsoform:147296] UniProt:P16092-3 Fgfr1 [Mus musculus] [ReferenceIsoform:403025] UniProt:P16092-1 Fgfr1 [Mus musculus] [ReferenceIsoform:8976474] UniProt:P16092-4 Fgfr1 [Mus musculus] [ReferenceIsoform:8976475] UniProt:P16092-5 Fgfr1 [Mus musculus] [ReferenceIsoform:8976476] UniProt:P16092-6 Fgfr1 [Mus musculus] |
| (referenceEntity) | [EntityWithAccessionedSequence:420339] Basic fibroblast growth factor receptor 1 [plasma membrane] [Mus musculus] [EntityWithAccessionedSequence:443254] Phospho (7 sites) FGFR1 [plasma membrane] [Mus musculus] |
| (referenceSequence) | [ModifiedResidue:443156] O4'-phospho-L-tyrosine at 654 [ModifiedResidue:443174] O4'-phospho-L-tyrosine at 730 [ModifiedResidue:443224] O4'-phospho-L-tyrosine at 653 [ModifiedResidue:443235] O4'-phospho-L-tyrosine at 583 [ModifiedResidue:443243] O4'-phospho-L-tyrosine at 585 [ModifiedResidue:443315] O4'-phospho-L-tyrosine at 766 [ModifiedResidue:443336] O4'-phospho-L-tyrosine at 463 |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:P16092 Fgfr1 (90401)
