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Symbol FGF1 contributors: mct/pgu - updated : 12-04-2016
HGNC name fibroblast growth factor 1 (acidic)
HGNC id 3665
Location 5q31.3      Physical location : 141.971.743 - 142.077.635
Synonym name
  • endothelial cell growth factor, alpha
  • endothelial cell growth factor, beta
  • heparin-binding growth factor 1 precursor
  • acidic fibroblast growth factor
  • Synonym symbol(s) FGFA, HBGF1, ECGF, ECGF-beta, ECGFA, ECGFB, FGF-alpha, GLIO703, AFGF, FGF-alpha
    TYPE functioning gene
    STRUCTURE 105.89 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • transcription is directed by at least three distinct promoters that are conserved across mammals
  • MAPPING cloned Y linked Y status confirmed
    Map cen - D5S490 - D5S500 - CD14 - D5S658 - FGF1 - PCDHA@ - PCDHB@ - PCDHG@ - APBB3 - HBEGF - D5S2374 - PFDN1 - D5S2119 - D5S2010 - DIAPH1 - TAF7 - D5S1979 - D5S352 - D5S147 - D5S178 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 3755 - 155 - 1992 1372643
  • proprotein
  • isoform 1
  • 4 - 3781 - 155 - 1992 1372643
  • proprotein
  • isoform 1
  • 5 - 3875 - 155 - 1992 1372643
  • proprotein
  • isoform 1
  • 3 - 4050 - 60 - 1992 1372643
  • isoform 2
  • 4 - 3669 - 155 - 1992 1372643
  • proprotein
  • isoform 1
  • 2 - 3516 - 59 - 1992 1372643
  • isoform 3
  • 4 - 4069 - 154 - 1992 1372643
    4 - 4072 - 155 - 1992 1372643
    4 - 3810 - 154 - 1992 1372643
    4 - 3813 - 155 - 1992 1372643
    5 - 3815 - 155 - 1992 1372643
    4 - 3828 - 155 - 1992 1372643
    4 - 3811 - 155 - 1992 1372643
    4 - 3679 - 154 - 1992 1372643
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly Homo sapiens
    Respiratoryrespiratory tracttrachea  highly
    Urinarykidney   highly Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadiposewhite   Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte Homo sapiens
    not specificadipocyte Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • N-terminal nuclear localization signal (NLS) implicated in the stimulation of DNA synthesis
  • two nuclear localization signals required for transport from the cytosol to the nucleus of externally added FGF-1 translocated into cells
  • a second putative NLS (NLS2), near the C-terminus,(a bipartite NLS consisting of two clusters of lysines separated by a spacer of 10 amino acids)
  • a IL1B-like domain
  • implication of FGF1 C-terminal domain on its intracellular activities
    interspecies homolog to murine Fgf1 (95.5pc)
    homolog to rattus Fgf1 (95.5pc)
  • heparin-binding growth factors family
  • fibroblast growth factor (FGF) family
  • CATEGORY protooncogene , signaling growth factor
        plasma membrane
  • phosphorylation occurs normally in the nucleus, and both NLS1 and NLS2 are important for efficient transport to the nucleus
  • under stress, FGF1 and S100A13 colocalize at the plasma membrane
  • upon stress, FGF1 is transported to the plasma membrane where it localizes prior to transmembrane translocation
  • basic FUNCTION
  • heparin binding growth factor
  • functioning as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor and mitogen for a variety of mesoderm- and neuroectoderm cells
  • involved in organogenesis, in cardiomyocyte proliferation and angiogenesis during development
  • perichondrial FGF1, FGF2, FGF6, FGF7, FGF9, FGF18, FGF21, fGF22 regulate growth plate chondrogenesis
  • potent inducer of cell migration and chemotaxis
  • activates spinal astrocytes, and activated astrocytes are implicated in neurodegenerative disorders such as amyotrophic lateral sclerosis
  • involved in opening pannexin and connexin hemichannels
  • stress-induced unconventional export of FGF1, is associated with and dependent on the formation of membrane blebs and localized cell surface exposure of phosphatidylserine
  • metabolic role for FGF1 as a critical transducer of PPARG signalling that mediates the proper coupling of nutrient storage to adaptive remodelling of adipose tissue
  • FGF1 and FGF2 play a critical role in angiogenesis, a formation of new blood vessels from existing blood vessels
  • induces maturation and cell cycle exit in chondrocytes, triggers rapid accumulation of RBL1-PPP2R2A complexes coinciding with RBL1 dephosphorylation
  • prolonged biological activity of FGF1 can be achieved by increasing its proteolytic resistance directly linked to improved global thermostability
  • acts through cell surface tyrosine kinase receptors, but FGF1 can also act directly in the cell nucleus, as a result of nuclear import of endogenously produced, non-secreted FGF1 or by transport of extracellular FGF1 via endosomes and cytosol into the nucleus
  • antidiabetes function of FGF1 may act partially through increasing beta-cell differentiation
  • role of intracellular FGF1 is to protect the cell against stress conditions by providing an additional signal for cell survival, independently of receptor-activated signaling cascades
  • lacking a secretion peptide signal and acting mainly in an intracellular and nuclear manner
    a component
  • PPARG-FGF1 axis is critical for maintaining metabolic homeostasis and insulin sensitization
  • Heparan sulfate (HS) chains form ternary complexes with FGF1/FGFR when enzymes carry out modifications in a specific manner
    small molecule
  • associated with S100A13 and p40 extracellular domain of synaptotagmin 1 (SYT1) for the release of signal peptide-less FGF1 in a temperature stress-induced pathway
  • directly interacts with integrins in a dose-dependent manner (with ITGAV)
  • interacting with S100A13 (released from the cells as a copper-dependent multiprotein complex that includes a small calcium-binding protein S100A13)
  • induces regulated intramembrane proteolysis (RIP) of FGFR3
  • both FGF19 and FGF21 but not FGF1 exhibit binding affinity to KLB
  • KPNA1, KPNB1 were required for nuclear import of FGF1
  • LRRC59 is strictly required for nuclear import of exogenous FGF1
  • nucleolin (NCL), a nuclear multifunctional protein, is an interaction partner of FGF1, and NCL-FGF1 interaction is critical for the intranuclear phosphorylation of FGF1 by PRKCD and thereby the regulation of nuclear export of FGF1
  • direct interaction of CTGF and FGF1, suggesting the co-presence of these molecules in the cartilage microenvironment
  • BGN binds to FGFR3c and FGF1
  • in heat-shocked cells, FGF1 and the C-terminal fragment of AHNAK2 colocalized with F-actin in the vicinity of the cell membrane
  • cell & other
    induced by temperature stress-induced pathway
    Phosphorylated by PRKCD (in the nucleus, FGF1 can be phosphorylated by PRKCD, and this event induces nuclear export of FGF1)
    Other accessible to pharmacologic regulation
    down-regulated by the binding of RFX1 to its promoter region
    induced in visceral (i.e. gonadal) white adipose tissue (WAT) in response to a high-fat diet
    phosphorylation does not regulate FGF1 neurotrophic activity but inhibits its anti-apoptotic activity after TP53-dependent apoptosis induction
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    results in diet-induced insulin resistance
  • to intracranial aneurysm
  • to Alzheimer disease(AD)
  • to variation of systolic Blood pressure
  • Variant & Polymorphism SNP
  • SNP at intron 4 increasing the risk of intracranial aneurysm
  • promoter polymorphism (-1385 A/G) was significantly associated with AD risk
  • SNP rs152524 was associated in a dose-dependent manner with systolic Blood pressure
  • Candidate gene
    Therapy target
    mutant R50E suppressed tumor growth while WT FGF1 enhanced it using cancer cells that stably express WT FGF1 or R50E
    FGF1/MAPK14 inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction
  • Fgf1 is highly induced in adipose tissue in response to high-fat diet (HFD) and mice lacking Fgf1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with HFD