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FLASH GENE
Symbol FGF2 contributors: mct/shn - updated : 08-02-2019
HGNC name fibroblast growth factor 2 (basic)
HGNC id 3676
DNA
TYPE functioning gene
STRUCTURE 71.53 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure
  • HOXA10 binds to two cis elements in the FGF2 promoter
    • MAPPING cloned Y linked N status confirmed
    Map cen - D4S1612 - D4S430 - FGF2 - D4S3250 - D4S2985 - qter
    RNA
    TRANSCRIPTS type messenger
    text
  • multiple polyadenylation sites on mRNA
  • five isoforms translated alternatively from AUG or CUG codon, CUG-initiated isorforms are located on nucleus and responsible fro intracrine effect, hwereas AUG-initiated isoform is mostly cytosolic and is responsible for paracrine and autocrine effects of FGF2
    • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 6774 - 288 - 1999 9858574
    - - - 18 - - 2015 26466960
  • cytosolic isoform
  • plays an unexpected role in the innate immune response
  • directly associated with inactivated DDX58 under physiological conditions, which enhanced DDX58 protein stability, thereby maintaining basal DDX58 levels
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly
    Endocrinethyroid   highly
    Hearing/Equilibriumearinnercochlea highly
    Nervousbrain   highly Homo sapiens
    Reproductivefemale systemuterus  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivecartilage   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell Homo sapiens
    Skeletonosteoblast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
    mono polymer monomer
    HOMOLOGY
    interspecies ortholog to Fgf2, Mus musculus
    ortholog to Fgf2, Rattus norvegicus
    ortholog to FGF2, Pan troglodytes
    ortholog to fgf2, Danio rerio
    Homologene
    FAMILY
  • heparin-binding fibroblast growth factor family
  • FGF1 subfamily
    • CATEGORY transcription factor , protooncogene , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • plays a specific role in cortical neurogenesis and skin wound healing (
  • inducer of anteroposterior neural pattern
  • essential for FGF8 and FGF10 reciprocal regulation loop in limb induction in mouse
  • involved in angiogenesis (myocardial cell proliferation)
  • enhancing the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells
  • required for a full proliferative response
  • inhibiting bone mineralization
  • stimulating cell proliferation
  • reduced the TAZ protein expression level in osteoblast-like cells
  • perichondrial FGF1, FGF2, FGF6, FGF7, FGF9, FGF18, FGF21, fGF22 regulate growth plate chondrogenesis
  • inducing the transient activation of JNK and stimulating the proliferation of mesenchymal stem cells
  • regulating the stability of nuclear bodies
  • negatively regulates angiogenin expression and contributes to the overall cell proliferation in H7402 hepatoma cells
  • have a role in high glucose-altered molecular signaling in pathogenesis of diabetic renal disease contributes to HeLa cells proliferation by affecting the expression of angiogenin
  • expression in tumor cell is an independent negative prognostic factor and coexpression of FGF2/VEGFR3 is strongly associated with poor survival in non small cell lung carcinomas
  • EGF and FGF2, may play an important role in the fate decision of neural crest progenitors and in the development of the peripheral nervous system
  • implicated in the control of adult neurogenesis based on changes in proliferation and fate choice of adult neural progenitor cells
  • plays a role in inducing osteoblastic differentiation of VSMCs by activating RUNX2 through MAPK-dependent- and oxidative stress-sensitive-signaling pathways
  • mediates PRSS50 downregulation by ERK activation, leading to the phosphorylation of Sp1 in this process)
  • promotes MSX2 stimulated ENPP1 expression via FRS2/MAPK signaling
  • has been implicated in the control of adult neurogenesis based on changes in proliferation and fate choice of adult neural progenitor cells
  • potential central role for the FGF2/NUDT6 antisense transcript in the ovarian follicle assembly process
  • activates JNK signaling pathway and may be partly responsible for the downregulation of keratocan and lumican expression in activated corneal keratocytes during corneal stromal wound healing (
  • enhances APP phagocytosis in primary microglia and inhibits APP production from primary neurons
  • enhances chondrogenesis of mesenchymal stem cells
  • FGF2 may influence at least two aspects of mesenchymal stem cells chondrogenesis
  • FGF2 inhibits osteoblastic differentiation of mesenchymal stem cells (HMSCs)
  • is expressed during the bone healing process of fractures and surgery bone sites
  • FGF1 and FGF2 play a critical role in angiogenesis, a formation of new blood vessels from existing blood vessels
  • histone acetylation and additional chromatin modifiers are important in determining the relative levels of FGF2 and NUDT6, supporting a model in which epigenetic remodeling contributes to their relative expression levels
  • FGF2 and NUDT6 in the regulation of cell transformation and cell cycle progression
  • role of FGF2 in innate immune response
  • abundant growth factor in the brain, exerting multiple functions on neural cells ranging from cell division, cell fate determination to differentiation
  • VEGFA and FGF2 are potent pro-angiogenic factors and play a critical role in cancer development and progression
  • FGF2 was superior, stimulating cell infiltration and angiogenesis better than TNFSF10 and VEGFA
  • is a mitogen that induces proliferation, differentiation, and migration of cells, as well as angiogenesis and carcinogenesis via autocrine or paracrine actions
  • airway smooth muscle cells (ASMCs)-derived FGF2 is a factor needed for lymphocyte-derived membrane conduits (LMCs) formation by CD4 T cells, affecting intercellular communication
    • CELLULAR PROCESS cell cycle, division, mitosis
    cell life, differentiation
    cell life, proliferation/growth
    cell migration & motility
    PHYSIOLOGICAL PROCESS development , angiogenesis
    text
  • limb, nervous development
  • mitogenic and angiogenic activities
  • an important modulator of cartilage and bone growth and differentiation (
    • PATHWAY
    metabolism
    signaling signal transduction
  • role for the GPC5-FGF2 pathway in nephrotic syndrome pathogenesis
  • oncogenic pathway that functionally links FGF2 with EZH2 via KDM2B and miR-101
    • a component
  • complex with FGFBP1, FGF1
  • LCOR and TRIM28 form a complex with ZNF350 on an intronic binding site in GADD45A gene and a novel site in the fibroblast growth factor 2 (FGF2) gene
    • INTERACTION
    DNA
    RNA
    small molecule other,
  • heparin binding
    • protein
  • protein kinase CKII (
  • Platelet factor 4, PF4 (
  • ribosomal protein L6/TAXREB107 (
  • Fibroblast growth factor receptor 1, FGFR1 (
  • fibroblast growth factor-2 (FGF-2)-interacting-factor, FIF (
  • FGFR5 beta Fc and R5 gamma Fc (
  • Fibroblast growth factor-binding protein 1, FGFBP1 (
  • CXCL13 (
  • ribosomal protein S19 (
  • Human basement membrane heparan sulfate proteoglycan, HSPG (
  • glypican 3, GPC3 (
  • Translokin (
  • neuropilin-1, Npn-1 (
  • nuclear active 90-kDa ribosomal S6 kinase 2, RSK2 (
  • Pentraxin 3, PTX3 (
  • thrombospondin-1 type III repeats (
  • CEP57 (
  • GPC1 (
  • induces ENPP1 expression in calvarial pre-osteoblasts and this occurs via a transcriptional mechanism involving RUNX2
  • may be a downstream effecter of FGF2, promoting cell proliferation and protecting from apoptosis
  • interacting with DACH1 (loss of DACH1 increases the number of tumor-initiating cells through transcriptional activation of FGF2)
  • interacting with PTH (anabolic action of PTH on bone formation requires FGF2)
  • ATF4may be a down stream target of FGF2 signaling in osteoblasts
  • FGF2 expression and secretion are regulated in a HOXA10-dependent manner in myeloid progenitor cells and differentiating phagocytes
  • in the tumor microenvironment, the reciprocal interplay between FGF2 and VEGFC collaboratively stimulated tumor growth, angiogenesis
  • FGF2 and CDX4 are direct target genes of HOXA10 and HOXA10 is a CDX4 target gene
  • FGF2 inhibited BMP2 and BMP4 expressions in HMSC
  • FGF2 can modulate BMP pathway in HMSCs by down-regulating BMP/BMPR expression, thereby inhibiting the osteoblastic differentiation of HMSCs
  • FGF2 increases IBSP transcription by targeting the FRE and AP1 elements in the proximal promoter of the human IBSP gene
  • FGF16 prevents potentially angiotensin II-induced cardiac hypertrophy and fibrosis by antagonizing FGF2
  • may have a negative regulatory role during elastic fiber assembly, perhaps in displacing elastin microassemblies from complexes with FBLN5 and/or cell surface heparan sulfate proteoglycans
  • FGF2-triggered protection of cardiac subsarcolemmal mitochondria from calcium overload is mitochondrial GJA1-dependent
  • DNM2 dependent endocytosis of FGFR1 is required for angiogenesis in response to FGF2 and the non-classical FGF ligand, FGF21
  • ATP1A1 is a recruitment factor for FGF2 at the inner leaflet of plasma membranes that may control phosphatidylinositol 4,5-bisphosphate-dependent membrane translocation as part of the unconventional secretory pathway of FGF2
  • FGF2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage
  • LTBP2 is a potent inhibitor of FGF2 that may influence FGF2 bioactivity during wound repair particularly in fibrotic tissues
  • FGF2 may be redirecting fibroblasts towards an anti-fibrotic phenotype by overriding TGFB1 mediated ITGA11 expression
  • during DDX58 activation induced by viral RNA, cytosolic FGF2 bound to the caspase recruitment domains of activated DDX58, which blocked DDX58-MAVS complex formation
  • FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1
  • FGF2, a growth factor commonly used to promote self-renewal in Mesenchymal stem cells (MSCs), rapidly induces HMGA2 expression in a time- and concentration-dependent manner
  • FGF2 is an extracellular inducer of NR2F2 expression and may suppress the osteogenic potential of mesenchymal cells by inducing NR2F2 expression prior to the onset of osteogenic differentiation
  • suppression of FGF2 by ETS2 repressor factor (ERF) is required for chorionic trophoblast differentiation
  • LOX propeptide promotes adipogenesis through inhibition of FGF2 signaling
  • GNA14 distinctively mediates fetoplacental endothelial cell migration and permeability in response to FGF2 and VEGFA
    • cell & other
    REGULATION
    activated by apomorphine (APO stimulates the FGF2 promoter via the MZF1 transcription factor)
    Human basement membrane heparan sulfate proteoglycan, HSPG (
    induced by mechanical stress in osteogenic cells
    inhibited by CXCL13 (
    Pentraxin 3, PTX3 (
    repressed by HDAC5
    Phosphorylated by protein kinase CK2 (
    Other FGF2 expression is under the control of an antisense transcript (see NUDT6)
    regulated by PTTG1
    upregulated by prostaglandin E2
    is regulated endogenously by an overlapping antisense gene called Nudix-type motif 6 (NUDT6)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in ovarian, testicular, breast cancer
    constitutional     --over  
    overproduced in idiopathic pulmonary hypertension (IPH) and contributes to SMC hyperplasia in IPH
    constitutional     --over  
    in the AD brain
    constitutional     --low  
    FGF2 expression is decreased in HOXA10-deficient cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativehuntington chorea
    potential therapy target in Huntington disease
    neurologyneurodegenerative 
    virus-mediated FGF2 gene delivery has potential as an alternative therapy of Alzheimer disease and possibly other neurocognitive disorders
    ANIMAL & CELL MODELS
  • mice lacking FGF2 are viable and fertile but display abnormalities in the cytoarchitecture of the neocortex, most pronounced in the frontal motor-sensory area, and a significant reduction in neuronal density in most layers of the motor cortex (
  • FGF-2-deficient mice display cerebral cortex defects at birthectopic parvalbumin-positive neurons are present in the hippocampal commissure and neuronal deficiencies are observed in the cervical spinal cord, and are hypotensive (
  • markedly reduced platelike trabecular structures, lost of many connecting rods of trabecular bone are, and a profound decreased mineralization of bone marrow stromal cultures in the Fgf2(-/-) mice (
  • anabolic action of PTH on bone formation is impaired in Fgf2-/- mice compared to wild type
  • Fgf2(-/-) mice exhibited decreased thermal pain sensitivity in the hotplate-test