Q04589 (FGFR1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 128. History...
Names and origin
|Protein names||Recommended name:|
Fibroblast growth factor receptor 1
Basic fibroblast growth factor receptor 1
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||822 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Tyrosine-protein kinase that acts as 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.
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
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.
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). 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 (via C-terminus) with NEDD4 (via WW3 domain). Interacts with KL By similarity. Interacts with SHB (via SH2 domain) and GRB10. Interacts with KAL1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2. Interacts with SOX2 and SOX3 By similarity. Ref.2
Cell membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm › cytosol. Cytoplasmic vesicle By similarity. Note: 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 By similarity. Ref.2
Expressed in the parathyroid. Ref.3
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.
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.
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.
N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus By similarity.
Contains 3 Ig-like C2-type (immunoglobulin-like) domains.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 21||21||Potential|
|Chain||22 – 822||801||Fibroblast growth factor receptor 1||PRO_0000016782|
|Topological domain||22 – 376||355||Extracellular Potential|
|Transmembrane||377 – 397||21||Helical; Potential|
|Topological domain||398 – 822||425||Cytoplasmic Potential|
|Domain||25 – 119||95||Ig-like C2-type 1|
|Domain||158 – 246||89||Ig-like C2-type 2|
|Domain||255 – 357||103||Ig-like C2-type 3|
|Domain||478 – 767||290||Protein kinase|
|Nucleotide binding||484 – 490||7||ATP By similarity|
|Nucleotide binding||562 – 564||3||ATP By similarity|
|Region||160 – 177||18||Heparin-binding|
|Active site||623||1||Proton acceptor By similarity|
|Binding site||514||1||ATP By similarity|
|Binding site||568||1||ATP By similarity|
|Binding site||627||1||ATP By similarity|
|Binding site||641||1||ATP By similarity|
|Site||766||1||Mediates interaction with PLCG1 and SHB By similarity|
Amino acid modifications
|Modified residue||463||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||583||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||585||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||653||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||654||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||730||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||766||1||Phosphotyrosine; by autocatalysis By similarity|
|Glycosylation||77||1||N-linked (GlcNAc...) Potential|
|Glycosylation||117||1||N-linked (GlcNAc...) Potential|
|Glycosylation||227||1||N-linked (GlcNAc...) Potential|
|Glycosylation||240||1||N-linked (GlcNAc...) Potential|
|Glycosylation||264||1||N-linked (GlcNAc...) Potential|
|Glycosylation||296||1||N-linked (GlcNAc...) Potential|
|Glycosylation||317||1||N-linked (GlcNAc...) Potential|
|Glycosylation||330||1||N-linked (GlcNAc...) Potential|
|Disulfide bond||55 ↔ 101||By similarity|
|Disulfide bond||178 ↔ 230||By similarity|
|Disulfide bond||277 ↔ 341||By similarity|
|||"The structure and expression of the FGF receptor-1 mRNA isoforms in rat tissues."|
Yazaki N., Hiroko F., Mitsuhiro O., Toshisuke K., Nobuyuki I.
Biochim. Biophys. Acta 1172:37-42(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling."|
Hu Y., Fang X., Dunham S.M., Prada C., Stachowiak E.K., Stachowiak M.K.
J. Biol. Chem. 279:29325-29335(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RPS6KA1, SUBCELLULAR LOCATION.
|||"The parathyroid is a target organ for FGF23 in rats."|
Ben-Dov I.Z., Galitzer H., Lavi-Moshayoff V., Goetz R., Kuro-o M., Mohammadi M., Sirkis R., Naveh-Many T., Silver J.
J. Clin. Invest. 117:4003-4008(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
|+||Additional computationally mapped references.|
|D12498 mRNA. Translation: BAA02059.1.|
|RefSeq||NP_077060.1. NM_024146.1. |
3D structure databases
|SMR||Q04589. Positions 25-119, 150-359, 464-765. |
Protein-protein interaction databases
|IntAct||Q04589. 3 interactions.|
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:620713. rat. |
|RGD||620713. Fgfr1. |
Enzyme and pathway databases
|BRENDA||18.104.22.168. 5301. |
Gene expression databases
Family and domain databases
|Gene3D||22.214.171.124. 3 hits. |
|InterPro||IPR028174. FGF_rcpt_1. |
|PANTHER||PTHR24416:SF131. PTHR24416:SF131. 1 hit. |
|Pfam||PF07679. I-set. 3 hits. |
PF07714. Pkinase_Tyr. 1 hit.
|PIRSF||PIRSF000628. FGFR. 1 hit. |
|PRINTS||PR00109. TYRKINASE. |
|SMART||SM00408. IGc2. 3 hits. |
SM00219. TyrKc. 1 hit.
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|PROSITE||PS50835. IG_LIKE. 3 hits. |
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
|Accession||Primary (citable) accession number: Q04589|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families