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FLASH GENE
Symbol FGFR1 contributors: mct - updated : 28-02-2017
HGNC name fibroblast growth factor receptor 1
HGNC id 3688
Corresponding disease
CRS7A craniosynostosis, syndromatic 7
ECCL encephalocraniocutaneous lipomatosis
HRTFDS Hartsfield syndrome
KAL2 Kallmann syndrome 2
NIHH normosmic idiopathic hypogonadotropic hypogonadism
OGD osteoglophonic dysplasia
SCLLS stem-cell leukemia/lymphoma syndrome
Location 8p11.22      Physical location : 38.268.656 - 38.326.352
Synonym name
  • FMS-like tyrosine kinase 2
  • basic fibroblast growth factor receptor 1
  • heparin-binding growth factor receptor
  • hydroxyaryl-protein kinase
  • fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome)
    • Synonym symbol(s) FGFRA, FLT2, CEK, FLG, BFGFR, C-FGR, CD331, H2, H3, H4, H5, KAL2, N-SAM
    EC.number 2.7.1.112, 2.7.10.1
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 57.70 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure three potential Sp factor binding sites located at 49 bp, 68 bp, and 100 bp upstream from the 3 prime end of the promoter segment
  • two non-consensus E2F binding sequences at positions + 4 to + 22 and + 25 to + 43 critical for E2F-1-mediated transactivation of FGFR 1 promoter
    • MAPPING cloned Y linked N status provisional
    Map see CEBPD
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 5963 - 812 - 1991 1650441
    18 - 5895 - 820 - 1991 1650441
    18 - 5917 91.9 822 - 1991 1650441
    using exon 9
    18 splicing 5911 - 820 - 1991 1650441
    two missing AAs Arg-Met
    17 splicing 5650 - 733 - 1991 1650441
    lacking the first Ig domain (exon 3)
    17 splicing 5644 - 730 - 1991 1650441
    lacking exon 3 Arg-Met
    18 - 5215 - 820 - 1991 1650441
    17 - 4954 - 733 - 1991 1650441
    19 - 5375 - 853 - 1991 1650441
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Nervousgangliasensory gangliadorsal root highly Homo sapiensAdult
    Reproductivefemale systemovary  highly
    Respiratoryrespiratory tracttrachea  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Muscularstriatumcardiac   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Muscularmyocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text endothelial stem/progenitor cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal peptide
  • three Ig-like C2 type extracellular domains
  • an acid box and heparin binding region between the first and second Ig loops
  • a single membrane-spanning segment
  • an intracellular split tyrosine-kinase domain at the C-terminus, and a C-terminal fragment of FGFR1, generated by receptor activation-dependent cleavage, which traffics to the nucleus and regulates the expression of target genes
    • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Fgfr1
    intraspecies homolog to fibroblast growth factor receptor 1(flg/fms related gene)
    Homologene
    FAMILY
  • fibroblast growth factor receptor family
    • CATEGORY enzyme , receptor membrane tyrosine kinase
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • full-length FGFR1 (120 kD) is in the plasma membrane/organelle fraction and a truncated FGFR1 fragment (55–60 kD) in the nuclear fraction; localized to the nucleus specifically in breast cancer cells that invaded into the stroma, and this invasion was impaired significantly by blocking FGFR signaling
    • basic FUNCTION
  • receptor tyrosine kinase, class IV, fibroblast growth factor receptor 1 (receptor for acidic FgF) involved in limb induction
  • playing a role in the modulation of bone elongation
  • mediate two independent signaling pathways in retinal pigment epithelial cells
  • regulates proliferation, differentiation, and maintenance of normal myocardium
  • playing a role in rhabdomyosarcoma tumorigenesis and a possible association with the deregulation of proliferation and differentiation of skeletal myoblasts in rhabdomyosarcoma
  • negatively regulates endothelial cell function by altering the balance of modulatory cytokines
  • with FGFR2 in kidney mesenchyme, are critical for normal early renal development
  • FGFR1, FGFR2, FGFR3, differentially control the normal generation of oligodendrocyte progenitor (OLP) from the embryonic ventral forebrain
  • internalization of FGFR1 controls axon growth and morphology of adult sensory neurons via selective activation of intracellular signaling pathways
  • clathrin-mediated endocytosis is required for efficient internalization and downregulation of FGFR1
  • initiates MAPK signaling, whereas SDC4-dependent FGFR1 macropinocytosis modulates the kinetics of MAPK activation
  • adipose FGFR1 regulates lipid metabolism through direct effect on adipose tissue and indirect effects on liver under starvation conditions that cause hepatic stress
  • crucial for breast cancer cell proliferation and tumor growth and angiogenesis
  • play an important role in many signalling cascades
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS ossification
    text bone development and maintenance
    PATHWAY
    metabolism
    signaling
  • FGF21/KLB/FGFR1 signaling plays an essential role in GnRH biology, potentially linking metabolism with reproduction
    • a component
  • forms a multi-protein complex with MTOR in vascular smooth muscle cells
  • GRB14 was recruited to FGFR1 into a trimeric complex containing also phospholipase C gamma (PLCG1)
  • homodimerization of FGFR1 appear to be a fundamental mechanism for the agonist activity of all FGF ligands at least in the case of the MAPK signaling
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • specific interaction between phosphorylated Y463 in FGFR1 with the CRKL SH2 domain
  • link between FGFR1 and the cell adhesion molecule neurofascin
  • interacting with FLRT1 (critical role of FLRT1 phosphorylation in the interdependent regulation of FLRT1 function and FGF receptor signalling)
  • NEDD4 is an E3 ubiquitin ligase regulating endocytosis and signalling of FGFR1
  • FGFR1 is a substrate for the serine protease GZMB, and endogenous GZMB can play a promigratory role, at least in part through cleaving FGFR1
  • LRIT3 is a regulator of the FGFR1
  • FGF21 effects on chondrocyte function are specific and depend on the normal activity of the FGFR1 and MAPK3
  • by binding FGFR1 and/or FGFR3, FGF21 prevents GH-mediated stimulation of chondrocyte proliferation and differentiation
  • correlation between PAR1 and FGFR1 suggests an association of the two receptors with a more aggressive breast cancer phenotype and, consequently, a potential role during tumor progression
  • PARK7 stimulates the differentiation of human mesenchymal stem cells to osteoblasts and induces angiogenesis in endothelial cells through activation of FGFR1 signalling
  • KLF10 interacts with the FGFR1 promoter, repressing its activity and cell proliferation
  • stimulates bone regeneration by inducing osteogenesis and angiogenesis via regulating FGFR1 signaling
  • RPS6KA3 is a potential FGFR1 interaction partner
  • DNM2 dependent endocytosis of FGFR1 is required for angiogenesis in response to FGF2 and the non-classical FGF ligand, FGF21
  • ESYT2 and ESYT3, but not ESYT1, selectively interact with activated FGFR1
  • MAP3K4 acts as a critical node to integrate FGF20-FGFR1 signaling responses to specifically influence hair cells (HCs) development
    • cell & other
    REGULATION
    activated by homodimerization in the presence of both the FGF agonist ligand and heparan sulfate glycosaminoglycan
    Other regulated by the pRB/E2F pathway
    its expression itself is regulated by FGF8 and FGF signaling, which may be of importance in breast tumors expressing FGFs at a high level
    ASSOCIATED DISORDERS
    corresponding disease(s) CRS7A , SCLLS , OGD , KAL2 , NIHH , HRTFDS , ECCL
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with FOP in t(6;8)(q27;p11),with CEP1 in t(8;9)(p11;q33), with ZNF198 in t(8;13)(p11;q12)
    tumoral somatic mutation      
    aberrant alternative splicing in glioblastoma (exon skipping)
    tumoral fusion      
    with BCR in t(8;22) (p11;q11)
    tumoral   amplification    
    during the progression of in situ to invasive breast carcinoma
    tumoral       gain of function
    in the 8p11 myeloproliferative syndrome
    tumoral fusion      
    with TIF1 in t(7;8)(q34;p11)in myeloproliferative syndrome
    tumoral fusion      
    with TNS3 in t(7;8) (p12.3;p11.2)in Kallmann syndrome with cleft lip and cleft palate
    tumoral fusion      
    to CPSF6, in t(8;12)(p11;q15) and the 8p11 myeloproliferative syndrome
    constitutional     --other  
    dysfunction (expression) of the FGFR1, SOS1 and RAF1 genes is involved in the development of unilateral or bilateral cryptorchidism
    tumoral     --over  
    in renal cell carcinoma
    tumoral fusion      
    NTRK2 is a new gene fusion target in pilocytic astrocytoma (fusion with QKI, FGFR1)
    tumoral fusion      
    to the transforming acidic coiled-coil (TACC) coding domains of TACC1 or TACC3, respectively in glioblastoma
    tumoral fusion      
    fusion FGFR1/TPR in 8p11 myeloproliferative syndrome
    tumoral fusion      
    ZMYM2-FGFR1 fusion in myeloproliferative syndrome
    tumoral   amplification    
    in squamous lung carcinomas
    Susceptibility
    Variant & Polymorphism SNP SNP g.8592931G-->C was found to have a significant negative correlation with the cephalic index for all populations
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS