Atlas of Genetics and Cytogenetics in Oncology and Haematology

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FGFR1 (Fibroblast Growth Factor Receptor 1)

Identity

Other namesBFGFR (basic fibroblast growth factor receptor)
FLT2 (FMS-like tyrosine kinase 2)
FLG (FMS-like gene)
CEK
FGFBR
N-SAM
HGNC FGFR1
Location 8p12
 
  FGFR1 (8p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

DNA/RNA

Transcription 2.7 mRNA

Protein

 
  Protein Diagram
Description 822 amino acids; 100-135 kDa glycoprotein from a 90-115 kDa protein core; tyrosine kinase receptor; contains four major domains: an extracellular domain with 2 or 3 Ig-like loops, a transmembrane domain and an intracellular domain , a juxtamembrane domain, and an intracellular domain composed of the tyrosine kinase domain (two kinase domains interrupted by a short kinase insert), and a C-terminal tail.
Localisation plasma membrane
Function FGF receptor with tyrosine kinase activity; binding of ligand (FGF)) in association with heparan sulfate proteoglycans induces receptor dimerization, autophosphorylation and signal transduction
Homology with other FGFR (FGFR2, FGFR3, and FGFR4)

Implicated in

Entity stem-cell myeloproliferative disorder associated with chromosomal translocations involving 8p12; to date, seven FGFR1 partners have been described (see below)
Disease stem-cell myeloproliferative disorder characterized by T- or B-cell lymphoblastic leukemia/lymphoma, myeloid hyperplasia, and peripheral blood eosinophilia, and it generally progresses to acute myeloid leukemia; specific to the 8p12 chromosomal region
Prognosis very poor (median survival: 12 mths)
Cytogenetics the 7 translocations are:
  • t(6;8)(q27; p12) involving FOP (FGFR1 Oncogene Partner)
  • t(8;9)(p12;q33) involving CEP110 (Centrosome protein 110)
  • t(8;11)(p12;p15)
  • t(8;12)(p12;q15)
  • t(8;13)(p12;q12 ) involving FIM (Fused In Myeloproliferative disorder also called ZNF198 or RAMP)
  • t(8;17)(p12;q25)
  • t(8;19)(p12;q13.3)
    additional anomalies: in the t(8;9)(p12;q33): +der(9), +21; in the t(8;13)(p12;q12): +8, +der(13), +21
    •  
    Hybrid/Mutated Gene
  • 5' FOP - 3' FGFR1 in the t(6;8)
  • 5'CEP110 - FGFR1 in the t(8;9)
  • 5' FIM/ZNF198 - 3' FGFR1 in the t(8;13)
    • Abnormal Protein three fusion transcripts are identified: FOP-FGFR1, CEP110-FGFR1, and FIM-FGFR1; they encode large proteins containing the N-term of either FOP or CEP110, or FIM, and the catalytic domain of FGFR1 at their C-term:
  • N-term leucine-rich region from FOP fused to the catalytic domain of FGFR1
  • N-term leucine zipper motifs from CEP110 fused to the catalytic domain of FGFR1
  • N-term zinc fingers from FIM fused to the Tyrosine kinase domain of FGFR1in C-term
    • Oncogenesis constitutive activation of FGFR1
      
    Entity Pfeiffer syndrome (inborn disease)
    Disease one form of Pfeiffer syndrome, an autosomal dominant craniosynostosis syndrome with broad thumbs and usually no mental deficiency, is due to a mutation in amino acid 252 (Pro252Arg substitution) of FGFR1
      
    Entity Breast cancer
    Disease gene amplification and overexpression in sporadic breast tumors
      

    Breakpoints

     

    External links

    Nomenclature
    HGNCFGFR1   3688
    Entrez_GeneFGFR1  2260  fibroblast growth factor receptor 1
    Cards
    AtlasFGFR1113
    GeneCardsFGFR1
    EnsemblFGFR1 [Search_View]   ENSG00000077782 [Gene_View]
    GenatlasFGFR1
    GeneLynxFGFR1
    eGenomeFGFR1
    euGene2260
    Genomic and cartography
    GoldenPathFGFR1  -  8p12   chr8:38387813-38445509 -  8p12   [Description]    (hg18-Mar_2006)
    EnsemblFGFR1 - 8p12 [CytoView]
    NCBIMapview
    OMIMDisease map [OMIM]
    HomoloGeneFGFR1
    Gene and transcription
    GenbankAB208919 [ ENTREZ ]
    GenbankAF173898 [ ENTREZ ]
    GenbankAK001052 [ ENTREZ ]
    GenbankAK024388 [ ENTREZ ]
    GenbankAK094303 [ ENTREZ ]
    RefSeqNM_015850 [ SRS ]    NM_015850 [ ENTREZ ]
    RefSeqNM_023105 [ SRS ]    NM_023105 [ ENTREZ ]
    RefSeqNM_023106 [ SRS ]    NM_023106 [ ENTREZ ]
    RefSeqNM_023107 [ SRS ]    NM_023107 [ ENTREZ ]
    RefSeqNM_023108 [ SRS ]    NM_023108 [ ENTREZ ]
    RefSeqNM_023110 [ SRS ]    NM_023110 [ ENTREZ ]
    RefSeqNM_023111 [ SRS ]    NM_023111 [ ENTREZ ]
    RefSeqAC_000051 [ SRS ]    AC_000051 [ ENTREZ ]
    RefSeqAC_000140 [ SRS ]    AC_000140 [ ENTREZ ]
    RefSeqNC_000008 [ SRS ]    NC_000008 [ ENTREZ ]
    RefSeqNG_007729 [ SRS ]    NG_007729 [ ENTREZ ]
    RefSeqNT_007995 [ SRS ]    NT_007995 [ ENTREZ ]
    RefSeqNW_001839128 [ SRS ]    NW_001839128 [ ENTREZ ]
    RefSeqNW_923907 [ SRS ]    NW_923907 [ ENTREZ ]
    AceViewFGFR1 AceView - NCBI
    UnigeneHs.264887 [ SRS ]    Hs.264887 [ NCBI ]     HS264887 [ spliceNest ]
    Fast-db4006 (alternative variants)
    Protein : pattern, domain, 3D structure
    SwissProtP11362 [ SRS]    P11362 [ EXPASY ]     P11362 [ INTERPRO ]     P11362 [ UNIPROT ]
    PrositePS50835 IG_LIKE [ SRS ]    PS50835 IG_LIKE [ Expasy ]
    PrositePS00107 PROTEIN_KINASE_ATP [ SRS ]    PS00107 PROTEIN_KINASE_ATP [ Expasy ]
    PrositePS50011 PROTEIN_KINASE_DOM [ SRS ]    PS50011 PROTEIN_KINASE_DOM [ Expasy ]
    PrositePS00109 PROTEIN_KINASE_TYR [ SRS ]    PS00109 PROTEIN_KINASE_TYR [ Expasy ]
    InterproIPR016248 Fibroblast_GF_rcpt [ SRS ]    IPR016248 Fibroblast_GF_rcpt [ EBI ]
    InterproIPR013151 Ig [ SRS ]    IPR013151 Ig [ EBI ]
    InterproIPR007110 Ig-like [ SRS ]    IPR007110 Ig-like [ EBI ]
    InterproIPR013783 Ig-like_fold [ SRS ]    IPR013783 Ig-like_fold [ EBI ]
    InterproIPR013098 Ig_I-set [ SRS ]    IPR013098 Ig_I-set [ EBI ]
    InterproIPR003598 Ig_sub2 [ SRS ]    IPR003598 Ig_sub2 [ EBI ]
    InterproIPR000719 Prot_kinase_core [ SRS ]    IPR000719 Prot_kinase_core [ EBI ]
    InterproIPR017441 Protein_kinase_ATP_bd_CS [ SRS ]    IPR017441 Protein_kinase_ATP_bd_CS [ EBI ]
    InterproIPR001245 Tyr_pkinase [ SRS ]    IPR001245 Tyr_pkinase [ EBI ]
    InterproIPR008266 Tyr_pkinase_AS [ SRS ]    IPR008266 Tyr_pkinase_AS [ EBI ]
    CluSTrP11362
    PfamPF07679 I-set [ SRS ]    PF07679 I-set [ Sanger ]    pfam07679 [ NCBI-CDD ]
    PfamPF00047 ig [ SRS ]    PF00047 ig [ Sanger ]    pfam00047 [ NCBI-CDD ]
    PfamPF07714 Pkinase_Tyr [ SRS ]    PF07714 Pkinase_Tyr [ Sanger ]    pfam07714 [ NCBI-CDD ]
    SmartSM00408 IGc2 [EMBL]
    SmartSM00219 TyrKc [EMBL]
    ProdomPD000001 Prot_kinase[INRA-Toulouse]
    ProdomP11362 FGFR1_HUMAN [ Domain structure ]   P11362 FGFR1_HUMAN  [ sequences sharing at least 1 domain ]
    BlocksP11362
    PDB1AGW [ SRS ]    1AGW [ PdbSum ],   1AGW [ IMB ]   1AGW [ RSDB ]
    PDB1CVS [ SRS ]    1CVS [ PdbSum ],   1CVS [ IMB ]   1CVS [ RSDB ]
    PDB1EVT [ SRS ]    1EVT [ PdbSum ],   1EVT [ IMB ]   1EVT [ RSDB ]
    PDB1FGI [ SRS ]    1FGI [ PdbSum ],   1FGI [ IMB ]   1FGI [ RSDB ]
    PDB1FGK [ SRS ]    1FGK [ PdbSum ],   1FGK [ IMB ]   1FGK [ RSDB ]
    PDB1FQ9 [ SRS ]    1FQ9 [ PdbSum ],   1FQ9 [ IMB ]   1FQ9 [ RSDB ]
    PDB1XR0 [ SRS ]    1XR0 [ PdbSum ],   1XR0 [ IMB ]   1XR0 [ RSDB ]
    PDB2CR3 [ SRS ]    2CR3 [ PdbSum ],   2CR3 [ IMB ]   2CR3 [ RSDB ]
    PDB2FGI [ SRS ]    2FGI [ PdbSum ],   2FGI [ IMB ]   2FGI [ RSDB ]
    PDB3C4F [ SRS ]    3C4F [ PdbSum ],   3C4F [ IMB ]   3C4F [ RSDB ]
    HPRD00634
    Protein Interaction databases
    DIPP11362
    IntActP11362
    Polymorphism : SNP, mutations, diseases
    OMIM101600;123150;136350;147950    [ map ]   
    GENECLINICS101600;123150;136350;147950
    SNPFGFR1 [dbSNP-NCBI]  
    SNPNM_015850 [SNP-NCI]  
    SNPNM_023105 [SNP-NCI]  
    SNPNM_023106 [SNP-NCI]  
    SNPNM_023107 [SNP-NCI]  
    SNPNM_023108 [SNP-NCI]  
    SNPNM_023110 [SNP-NCI]  
    SNPNM_023111 [SNP-NCI]  
    SNPFGFR1 [GeneSNPs - Utah]  FGFR1] [HGBASE - SRS]
    HAPMAPFGFR1 [HAPMAP]  
    COSMICFGFR1 [Somatic mutation (COSMIC-CGP-Sanger)]  
    TICdbFGFR1 [Translocation breakpoints In Cancer]  
    HGMDFGFR1
    General knowledge
    Family BrowserFGFR1 [UCSC Family Browser]
    SOURCENM_015850
    SOURCENM_023105
    SOURCENM_023106
    SOURCENM_023107
    SOURCENM_023108
    SOURCENM_023110
    SOURCENM_023111
    SMDHs.264887
    SAGEHs.264887
    Enzyme2.7.10.1 [ Enzyme-Expasy ]   2.7.10.1 [ Enzyme-SRS ]   2.7.10.1 [ IntEnz-EBI ]   2.7.10.1 [ BRENDA ]   2.7.10.1 [ KEGG ]   2.7.10.1 [ WIT ]
    GOMAPKKK cascade [Amigo]  MAPKKK cascade
    GOnucleotide binding [Amigo]  nucleotide binding
    GOskeletal development [Amigo]  skeletal development
    GOreceptor activity [Amigo]  receptor activity
    GOfibroblast growth factor receptor activity [Amigo]  fibroblast growth factor receptor activity
    GOfibroblast growth factor receptor activity [Amigo]  fibroblast growth factor receptor activity
    GOprotein binding [Amigo]  protein binding
    GOATP binding [Amigo]  ATP binding
    GOmembrane fraction [Amigo]  membrane fraction
    GOplasma membrane [Amigo]  plasma membrane
    GOintegral to plasma membrane [Amigo]  integral to plasma membrane
    GOprotein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
    GOheparin binding [Amigo]  heparin binding
    GOfibroblast growth factor receptor signaling pathway [Amigo]  fibroblast growth factor receptor signaling pathway
    GOfibroblast growth factor receptor signaling pathway [Amigo]  fibroblast growth factor receptor signaling pathway
    GOcell growth [Amigo]  cell growth
    GOtransferase activity [Amigo]  transferase activity
    KEGGMAPK signaling pathway
    KEGGAdherens junction
    KEGGRegulation of actin cytoskeleton
    PubGeneFGFR1
    TreeFamFGFR1
    CTD2260 [Comparative ToxicoGenomics Database]
    Other databases
    Probes
    ProbeCancer Cytogenetics (Bari)
    ProbeFGFR1 Related clones (RZPD - Berlin)
    PubMed
    PubMed163 Pubmed reference(s) in LocusLink

    Bibliography

    Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor.
    Lee PL, Johnson DE, Cousens LS, Fried VA, Williams LT
    Science (New York, N.Y.). 1989 ; 245 (4913) : 57-60.
    PMID 2544996
     
    The complete amino acid sequence of the shorter form of human basic fibroblast growth factor receptor deduced from its cDNA.
    Itoh N, Terachi T, Ohta M, Seo MK
    Biochemical and biophysical research communications. 1990 ; 169 (2) : 680-685.
    PMID 2162671
     
    The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain.
    Johnson DE, Lu J, Chen H, Werner S, Williams LT
    Molecular and cellular biology. 1991 ; 11 (9) : 4627-4634.
    PMID 1652059
     
    cDNA cloning and expression of a human FGF receptor which binds acidic and basic FGF.
    Wennstrm S, Sandstrm C, Claesson-Welsh L
    Growth factors (Chur, Switzerland). 1991 ; 4 (3) : 197-208.
    PMID 1722683
     
    Structural and functional diversity in the FGF receptor multigene family.
    Johnson DE, Williams LT
    Advances in cancer research. 1993 ; 60 : 1-41.
    PMID 8417497
     
    FGFR activation in skeletal disorders: too much of a good thing.
    Webster MK, Donoghue DJ
    Trends in genetics : TIG. 1997 ; 13 (5) : 178-182.
    PMID 9154000
     
    Differential expression assay of chromosome arm 8p genes identifies Frizzled-related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate breast cancer genes.
    Ugolini F, Adlade J, Charafe-Jauffret E, Nguyen C, Jacquemier J, Jordan B, Birnbaum D, Pbusque MJ
    Oncogene. 1999 ; 18 (10) : 1903-1910.
    PMID 10086345
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    Contributor(s)

    Written03-1998Jean-Loup Huret
    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
    Updated12-2000Marie-Josèphe Pébusque
    INSERM U119, IFR 57, 27 Blvd Leï Roure, 13009 Marseille, France

    Citation

    This paper should be referenced as such :
    Huret JL . FGFR1 (Fibroblast Growth Factor Receptor 1). Atlas Genet Cytogenet Oncol Haematol. March 1998 .
    URL : http://AtlasGeneticsOncology.org/Genes/FGFR1113.html
    Pébusque MJ . FGFR1 (Fibroblast Growth Factor Receptor 1). Atlas Genet Cytogenet Oncol Haematol. December 2000 .
    URL : http://AtlasGeneticsOncology.org/Genes/FGFR1113.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Mon Aug 11 21:13:54 2008

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