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Q04589

- FGFR1_RAT

UniProt

Q04589 - FGFR1_RAT

Protein

Fibroblast growth factor receptor 1

Gene

Fgfr1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    Functioni

    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.By similarity

    Catalytic activityi

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

    Enzyme regulationi

    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.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei514 – 5141ATPPROSITE-ProRule annotation
    Binding sitei568 – 5681ATPPROSITE-ProRule annotation
    Active sitei623 – 6231Proton acceptorPROSITE-ProRule annotation
    Binding sitei627 – 6271ATPPROSITE-ProRule annotation
    Binding sitei641 – 6411ATPPROSITE-ProRule annotation
    Sitei766 – 7661Mediates interaction with PLCG1 and SHBBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi484 – 4907ATPPROSITE-ProRule annotation
    Nucleotide bindingi562 – 5643ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. cell adhesion molecule binding Source: RGD
    3. fibroblast growth factor-activated receptor activity Source: UniProtKB
    4. fibroblast growth factor binding Source: UniProtKB
    5. glycoprotein binding Source: RGD
    6. heparin binding Source: UniProtKB
    7. protein binding Source: IntAct
    8. protein complex binding Source: RGD

    GO - Biological processi

    1. central nervous system neuron development Source: RGD
    2. fibroblast growth factor receptor signaling pathway Source: UniProtKB
    3. motogenic signaling involved in postnatal olfactory bulb interneuron migration Source: RGD
    4. negative regulation of osteoblast differentiation Source: RGD
    5. neuron projection development Source: RGD
    6. peptidyl-tyrosine phosphorylation Source: UniProtKB
    7. positive regulation of cell proliferation Source: UniProtKB
    8. positive regulation of MAP kinase activity Source: UniProtKB
    9. positive regulation of mesenchymal cell proliferation Source: RGD
    10. positive regulation of neuron differentiation Source: UniProtKB
    11. positive regulation of neuron projection development Source: RGD
    12. positive regulation of phospholipase C activity Source: UniProtKB
    13. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    14. protein autophosphorylation Source: UniProtKB
    15. regulation of cell proliferation Source: RGD
    16. regulation of sensory perception of pain Source: RGD
    17. regulation of stem cell proliferation Source: RGD
    18. stem cell maintenance Source: RGD

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Heparin-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 5301.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Fibroblast growth factor receptor 1 (EC:2.7.10.1)
    Short name:
    FGFR-1
    Short name:
    bFGF-R-1
    Alternative name(s):
    Basic fibroblast growth factor receptor 1
    MFR
    Proto-oncogene c-Fgr
    CD_antigen: CD331
    Gene namesi
    Name:Fgfr1
    Synonyms:Flg
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi620713. Fgfr1.

    Subcellular locationi

    Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Nucleus 1 Publication. Cytoplasmcytosol 1 Publication. 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.By similarity

    GO - Cellular componenti

    1. cytoplasmic membrane-bounded vesicle Source: UniProtKB-SubCell
    2. cytosol Source: UniProtKB-SubCell
    3. integral component of membrane Source: UniProtKB-KW
    4. nucleus Source: UniProtKB-SubCell
    5. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2121Sequence AnalysisAdd
    BLAST
    Chaini22 – 822801Fibroblast growth factor receptor 1PRO_0000016782Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi55 ↔ 101PROSITE-ProRule annotation
    Glycosylationi77 – 771N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi117 – 1171N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi178 ↔ 230PROSITE-ProRule annotation
    Glycosylationi227 – 2271N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi240 – 2401N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi264 – 2641N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi277 ↔ 341PROSITE-ProRule annotation
    Glycosylationi296 – 2961N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi317 – 3171N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi330 – 3301N-linked (GlcNAc...)Sequence Analysis
    Modified residuei463 – 4631Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei583 – 5831Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei585 – 5851Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei653 – 6531Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei654 – 6541Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei730 – 7301Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei766 – 7661Phosphotyrosine; by autocatalysisBy similarity

    Post-translational modificationi

    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.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.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.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ04589.
    PRIDEiQ04589.

    Expressioni

    Tissue specificityi

    Expressed in the parathyroid.1 Publication

    Gene expression databases

    GenevestigatoriQ04589.

    Interactioni

    Subunit structurei

    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.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Htr1aP193276EBI-2480918,EBI-6570156
    Plcg1P106862EBI-2480918,EBI-520788

    Protein-protein interaction databases

    BioGridi249399. 1 interaction.
    IntActiQ04589. 3 interactions.
    MINTiMINT-1520059.

    Structurei

    3D structure databases

    ProteinModelPortaliQ04589.
    SMRiQ04589. Positions 25-119, 150-359, 464-765.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini22 – 376355ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini398 – 822425CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei377 – 39721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini25 – 11995Ig-like C2-type 1Add
    BLAST
    Domaini158 – 24689Ig-like C2-type 2Add
    BLAST
    Domaini255 – 357103Ig-like C2-type 3Add
    BLAST
    Domaini478 – 767290Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni160 – 17718Heparin-bindingAdd
    BLAST

    Domaini

    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.By similarity

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000263410.
    HOVERGENiHBG000345.
    KOiK04362.
    PhylomeDBiQ04589.

    Family and domain databases

    Gene3Di2.60.40.10. 3 hits.
    InterProiIPR028174. 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]
    PANTHERiPTHR24416:SF131. PTHR24416:SF131. 1 hit.
    PfamiPF07679. I-set. 3 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000628. FGFR. 1 hit.
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00408. IGc2. 3 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50835. IG_LIKE. 3 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q04589-1 [UniParc]FASTAAdd to Basket

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    MWGWRGLLFW AVLVTATLCT ARPAPTLPEQ AQPWGVPVEV ESLLVHPGDL    50
    LQLRCRLRDD VQSINWLRDG VQLAESNRTR ITGEEVEVRD SIPADSGLYA 100
    CVTNSPSGSD TTYFSVNVSD ALPSSEDDDD DDDSSSEEKE TDNTKPNRRP 150
    VAPYWTSPEK MEKKLHAVPA AKTVKFKCPS SGTPSPTLRW LKNGKEFKPD 200
    HRIGGYKVRY ATWSIIMDSV VPSDKGNYTC IVENEYGSIN HTYQLDVVER 250
    SPHRPILQAG LPANKTVALG SNVEFMCKVY SDPQPHIQWL KHIEVNGSKI 300
    GPDNLPYDQI LKTAGVNTTD KEMEVLHLRN VSFEDAGEYT CLAGNSIGLS 350
    HHSAWLTVLE ALEERPAVMT SPLYLEIIIY CTGAFLISCM VGSVIIYKMK 400
    SGTKKSDFHS QMAVHKLAKS IPLRRQVTVS ADSSASMNSG VLLVRPSRLS 450
    SSGTPMLAGV SEYELPEDPR WELPRDRLVL GKPLGEGCFG QVVLAEAIGL 500
    DKDKPNRVTK VAVKMLKSDA TEKDLSDLIS EMEMMKMIGK HKNIINLLGA 550
    CTQDGPLYVI VEYASKGNLR EYLQARRPPG LEYCYNPSHN PEEQLSSKDL 600
    VSCAYQVARG MEYLASKKCI HRDLAARNVL VTEDNVMKIA DFGLARDIHH 650
    IDYYKKTTNG RLPVKWMAPE ALFDRIYTHQ SDVWSFGVLL WEIFTLGGSP 700
    NPGVPVEELF KLLKEGHRMD KPSNCTNELY MMMRDCWNAV PSQRPTFKQL 750
    VEDLDRIVAL TSNQEYLDLS MPLDQDSPSF PDTRSSTCSS GEDSVFSHEP 800
    FPEEPCLPRH PTQLANGGLN RR 822
    Length:822
    Mass (Da):91,825
    Last modified:June 1, 1994 - v1
    Checksum:iE59D924D0A1DE5C5
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D12498 mRNA. Translation: BAA02059.1.
    PIRiS29840.
    RefSeqiNP_077060.1. NM_024146.1.
    UniGeneiRn.207203.
    Rn.9797.

    Genome annotation databases

    GeneIDi79114.
    KEGGirno:79114.
    UCSCiRGD:620713. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D12498 mRNA. Translation: BAA02059.1 .
    PIRi S29840.
    RefSeqi NP_077060.1. NM_024146.1.
    UniGenei Rn.207203.
    Rn.9797.

    3D structure databases

    ProteinModelPortali Q04589.
    SMRi Q04589. Positions 25-119, 150-359, 464-765.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 249399. 1 interaction.
    IntActi Q04589. 3 interactions.
    MINTi MINT-1520059.

    Proteomic databases

    PaxDbi Q04589.
    PRIDEi Q04589.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 79114.
    KEGGi rno:79114.
    UCSCi RGD:620713. rat.

    Organism-specific databases

    CTDi 2260.
    RGDi 620713. Fgfr1.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000263410.
    HOVERGENi HBG000345.
    KOi K04362.
    PhylomeDBi Q04589.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 5301.

    Miscellaneous databases

    NextBioi 614518.

    Gene expression databases

    Genevestigatori Q04589.

    Family and domain databases

    Gene3Di 2.60.40.10. 3 hits.
    InterProi IPR028174. 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 ]
    PANTHERi PTHR24416:SF131. PTHR24416:SF131. 1 hit.
    Pfami PF07679. I-set. 3 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000628. FGFR. 1 hit.
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00408. IGc2. 3 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50835. IG_LIKE. 3 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. Cited for: TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiFGFR1_RAT
    AccessioniPrimary (citable) accession number: Q04589
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: June 1, 1994
    Last modified: October 1, 2014
    This is version 135 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3