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Q04589 (FGFR1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fibroblast growth factor receptor 1

Short name=FGFR-1
Short name=bFGF-R-1
EC=2.7.10.1
Alternative name(s):
Basic fibroblast growth factor receptor 1
MFR
Proto-oncogene c-Fgr
CD_antigen=CD331
Gene names
Name:Fgfr1
Synonyms:Flg
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length822 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme 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 structure

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

Subcellular location

Cell membrane; Single-pass type I membrane protein. Nucleus. Cytoplasmcytosol. 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

Tissue specificity

Expressed in the parathyroid. Ref.3

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.

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.

Contains 3 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Cytoplasmic vesicle
Membrane
Nucleus
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Heparin-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcentral nervous system neuron development

Inferred from mutant phenotype PubMed 17314281. Source: RGD

fibroblast growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

limb development

Inferred from electronic annotation. Source: InterPro

motogenic signaling involved in postnatal olfactory bulb interneuron migration

Inferred from mutant phenotype PubMed 20083104. Source: RGD

negative regulation of osteoblast differentiation

Inferred from mutant phenotype PubMed 18690792. Source: RGD

neuron projection development

Inferred from direct assay PubMed 12791257. Source: RGD

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of MAP kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mesenchymal cell proliferation

Inferred from mutant phenotype PubMed 18690792. Source: RGD

positive regulation of neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron projection development

Inferred from direct assay PubMed 19952283. Source: RGD

positive regulation of phospholipase C activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 19229075. Source: BHF-UCL

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell proliferation

Inferred from direct assay PubMed 9763444. Source: RGD

regulation of sensory perception of pain

Inferred from mutant phenotype PubMed 17905520. Source: RGD

regulation of stem cell proliferation

Inferred from mutant phenotype PubMed 18690792. Source: RGD

stem cell maintenance

Inferred from mutant phenotype PubMed 19505325. Source: RGD

   Cellular_componentcytoplasmic membrane-bounded vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cell adhesion molecule binding

Inferred from physical interaction PubMed 19666467. Source: RGD

fibroblast growth factor binding

Inferred from sequence or structural similarity. Source: UniProtKB

fibroblast growth factor-activated receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

glycoprotein binding

Inferred from direct assay PubMed 19952283. Source: RGD

heparin binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 19665973PubMed 22035699PubMed 22553035. Source: IntAct

protein complex binding

Inferred from physical interaction PubMed 19339244. Source: RGD

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 822801Fibroblast growth factor receptor 1
PRO_0000016782

Regions

Topological domain22 – 376355Extracellular Potential
Transmembrane377 – 39721Helical; Potential
Topological domain398 – 822425Cytoplasmic Potential
Domain25 – 11995Ig-like C2-type 1
Domain158 – 24689Ig-like C2-type 2
Domain255 – 357103Ig-like C2-type 3
Domain478 – 767290Protein kinase
Nucleotide binding484 – 4907ATP By similarity
Nucleotide binding562 – 5643ATP By similarity
Region160 – 17718Heparin-binding

Sites

Active site6231Proton acceptor By similarity
Binding site5141ATP By similarity
Binding site5681ATP By similarity
Binding site6271ATP By similarity
Binding site6411ATP By similarity
Site7661Mediates interaction with PLCG1 and SHB By similarity

Amino acid modifications

Modified residue4631Phosphotyrosine; by autocatalysis By similarity
Modified residue5831Phosphotyrosine; by autocatalysis By similarity
Modified residue5851Phosphotyrosine; by autocatalysis By similarity
Modified residue6531Phosphotyrosine; by autocatalysis By similarity
Modified residue6541Phosphotyrosine; by autocatalysis By similarity
Modified residue7301Phosphotyrosine; by autocatalysis By similarity
Modified residue7661Phosphotyrosine; by autocatalysis By similarity
Glycosylation771N-linked (GlcNAc...) Potential
Glycosylation1171N-linked (GlcNAc...) Potential
Glycosylation2271N-linked (GlcNAc...) Potential
Glycosylation2401N-linked (GlcNAc...) Potential
Glycosylation2641N-linked (GlcNAc...) Potential
Glycosylation2961N-linked (GlcNAc...) Potential
Glycosylation3171N-linked (GlcNAc...) Potential
Glycosylation3301N-linked (GlcNAc...) Potential
Disulfide bond55 ↔ 101 By similarity
Disulfide bond178 ↔ 230 By similarity
Disulfide bond277 ↔ 341 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q04589 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: E59D924D0A1DE5C5

FASTA82291,825
        10         20         30         40         50         60 
MWGWRGLLFW AVLVTATLCT ARPAPTLPEQ AQPWGVPVEV ESLLVHPGDL LQLRCRLRDD 

        70         80         90        100        110        120 
VQSINWLRDG VQLAESNRTR ITGEEVEVRD SIPADSGLYA CVTNSPSGSD TTYFSVNVSD 

       130        140        150        160        170        180 
ALPSSEDDDD DDDSSSEEKE TDNTKPNRRP VAPYWTSPEK MEKKLHAVPA AKTVKFKCPS 

       190        200        210        220        230        240 
SGTPSPTLRW LKNGKEFKPD HRIGGYKVRY ATWSIIMDSV VPSDKGNYTC IVENEYGSIN 

       250        260        270        280        290        300 
HTYQLDVVER SPHRPILQAG LPANKTVALG SNVEFMCKVY SDPQPHIQWL KHIEVNGSKI 

       310        320        330        340        350        360 
GPDNLPYDQI LKTAGVNTTD KEMEVLHLRN VSFEDAGEYT CLAGNSIGLS HHSAWLTVLE 

       370        380        390        400        410        420 
ALEERPAVMT SPLYLEIIIY CTGAFLISCM VGSVIIYKMK SGTKKSDFHS QMAVHKLAKS 

       430        440        450        460        470        480 
IPLRRQVTVS ADSSASMNSG VLLVRPSRLS SSGTPMLAGV SEYELPEDPR WELPRDRLVL 

       490        500        510        520        530        540 
GKPLGEGCFG QVVLAEAIGL DKDKPNRVTK VAVKMLKSDA TEKDLSDLIS EMEMMKMIGK 

       550        560        570        580        590        600 
HKNIINLLGA CTQDGPLYVI VEYASKGNLR EYLQARRPPG LEYCYNPSHN PEEQLSSKDL 

       610        620        630        640        650        660 
VSCAYQVARG MEYLASKKCI HRDLAARNVL VTEDNVMKIA DFGLARDIHH IDYYKKTTNG 

       670        680        690        700        710        720 
RLPVKWMAPE ALFDRIYTHQ SDVWSFGVLL WEIFTLGGSP NPGVPVEELF KLLKEGHRMD 

       730        740        750        760        770        780 
KPSNCTNELY MMMRDCWNAV PSQRPTFKQL VEDLDRIVAL TSNQEYLDLS MPLDQDSPSF 

       790        800        810        820 
PDTRSSTCSS GEDSVFSHEP FPEEPCLPRH PTQLANGGLN RR 

« Hide

References

[1]"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].
[2]"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.
[3]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D12498 mRNA. Translation: BAA02059.1.
PIRS29840.
RefSeqNP_077060.1. NM_024146.1.
UniGeneRn.207203.
Rn.9797.

3D structure databases

ProteinModelPortalQ04589.
SMRQ04589. Positions 25-119, 150-359, 464-765.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249399. 1 interaction.
IntActQ04589. 3 interactions.
MINTMINT-1520059.

Proteomic databases

PaxDbQ04589.
PRIDEQ04589.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID79114.
KEGGrno:79114.
UCSCRGD:620713. rat.

Organism-specific databases

CTD2260.
RGD620713. Fgfr1.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000263410.
HOVERGENHBG000345.
KOK04362.
PhylomeDBQ04589.

Enzyme and pathway databases

BRENDA2.7.10.1. 5301.

Gene expression databases

GenevestigatorQ04589.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
InterProIPR028174. FGF_rcpt_1/4.
IPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PANTHERPTHR24416:SF131. PTHR24416:SF131. 1 hit.
PfamPF07679. I-set. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFPIRSF000628. FGFR. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio614518.

Entry information

Entry nameFGFR1_RAT
AccessionPrimary (citable) accession number: Q04589
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 11, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families