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FLASH GENE
Symbol FGFR1 contributors: mct - updated : 28-02-2016
HGNC name fibroblast growth factor receptor 1
HGNC id 3688
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 (5560 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
    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
  • 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
  • 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
    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