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FLASH GENE
Symbol FGF19 contributors: mct - updated : 21-03-2020
HGNC name fibroblast growth factor 19
HGNC id 3675
Location 11q13.3      Physical location : 69.513.006 - 69.519.106
Synonym symbol(s) FGF-19, FGF15
DNA
TYPE functioning gene
STRUCTURE 6.10 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 2157 - 216 - 2007 17623664
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinesmall intestineileum   Homo sapiens
 liver     Homo sapiens
Reproductivemale systemtestis   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivecartilage   
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal, pregnancy
Text brain
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal region of FGF19 (and, by extension, the N-terminal regions of the other subfamily members, as well) may interact directly with the D3 region of FGFR to achieve receptor specificity and activation
  • a signal sequence
  • two cysteine residues that are conserved in the FGF family
  • C-terminal tail necessary for its recognition of Klotho family proteins
  • HOMOLOGY
    Homologene
    FAMILY
  • heparin-binding growth factors family
  • FGF19 subfamily
  • CATEGORY signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
    text secreted from ileum and functions as an enterohepatic signal for the regulation of bile acid metabolism
    basic FUNCTION
  • fibroblast growth factor, heparin dependent ligand for FGFR4, potentially playing an important role in brain development
  • regulates bile acid homeostasis and metabolic state in an endocrine fashion
  • with KLB, repress apical sodium bile transporter in enterocytes and cholangiocytes
  • regulate energy, bile acid, glucose, lipid, phosphate, and vitamin D homeostasis in an endocrine fashion
  • regulating bile acid homeostasis and metabolic state in an endocrine fashion
  • secreted from ileum and functions as an enterohepatic signal to regulate bile acid homeostasis
  • having an effect on lipogenic enzyme expression that is correlated with alterations in NR0B2 expression
  • suppresses the stimulatory effect of insulin on the rate of fatty acid synthesis and the expression of lipogenic enzymes in hepatocytes
  • playing a physiological role in adult photoreceptor phenotypic maintenance and survival and argue in favor of its use as a neuroprotectant
  • with FGF21 share the ability to regulate glucose, lipid, and energy homeostasis
  • having both metabolic and proliferative effects
  • FGF19 and FGF21 can regulate glucose, lipid, and energy metabolism, while FGF23 regulates phosphate homeostasis
  • FGF19 is secreted from intestine upon feeding and acts on liver to suppress bile acid synthesis
  • brain is implicated in the antidiabetic action of systemic FGF19 and has capacity to rapidly, potently, and selectively increase insulin-independent glucose disposal
  • is likely the SHH downstream signal to control thalamic regionalization, neurogenesis, and neuronal differentiation by regulating the expression and mutual segregation of neurogenic and proneural regulatory genes
  • ileum-derived endrocrine factor that is produced in response to transepithelial bile salt flux
  • represses bile salt synthesis in the liver
  • regulation of Bile acid (BA) synthesis in response to cholestasis is primarily controlled by circulating FGF19 and that under cholestatic conditions, the FGF19-BA synthesis feedback mechanism remains intact
  • FGF19, FGF21 and FGF23 are circulating hormones that regulate critical metabolic processes in a variety of tissues, and FGF19 regulates bile acid synthesis and lipogenesis
  • activates Hippo signaling to suppress bile acid metabolism, liver overgrowth, and tumorigenesis
  • ileum-derived fibroblast growth factor 19 (FGF19) plays key roles in hepatic glucose homeostasis in animals in an insulin-independent manner
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • KLF15-FGF19 signalling axis that regulates circadian bile acid production
  • FGF19-FGFR4 signaling is implicated in many cellular processes including cell proliferation, migration, metabolism, and differentiation
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • increased the expression of small heterodimer partner (NR0B2), a transcriptional repressor that inhibits lipogenic enzyme expression via a SREBF1-independent mechanism
  • interacting with KLB (significantly increased the interactions between FGF19 and FGFR4)
  • interacting with FGFR4 (FGFR4 activation is the mechanism whereby FGF19 can increase hepatocyte proliferation and induce hepatocellular carcinoma formation)
  • FGFR4-extracellular domain might potentially neutralize FGF19
  • both FGF19 and FGF21 but not FGF1 exhibit binding affinity to KLB
  • SREBPF2 negatively regulates the NR1H4-mediated transcriptional activation of the FGF19 gene in human intestinal cells
  • KLF15 is the first endogenous negative regulator of circadian FGF15 expression, and this regulation has important implications for physiologic control of nutrient availability and metabolic homeostasis
  • SUFU controls cerebellar neuronal differentiation in a manner modulated by GLI3 repressor and FGF19
  • FGF19 induced an antioxidant response through stimulating the expression of nuclear erythroid factor 2 NFE2L2 and as well as reducing ROS production through the AMPK signaling pathway
  • KLB is an obligate coreceptor, mediating both fibroblast growth factor FGF19 and FGF21 signaling
  • NR1H4 plays a central role in maintaining bile acid (BA) homeostasis by transcriptional control of numerous enterohepatic genes, including intestinal FGF19, a hormone that strongly represses hepatic BA synthesis
  • FGFR4 plays a critical role in cancer progression and metastasis, particularly in those cancer patients who have FGF19 amplification
  • interaction between FGF19 and FGFR4 plays an essential role in colorectal tumorigenesis
  • cell & other
    REGULATION
    induced by NR1H4 that activates Hippo signaling to suppress bile acid metabolism, liver overgrowth, and tumorigenesis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colon adenocarcinoma cell line
    constitutional     --over  
    in the liver of patients with extrahepatic cholestasis
    constitutional     --low  
    decrease of FGF19 contributes to the increase of fasting glucose in human in an insulin-independent manner
    tumoral   amplification    
    FGF19 gene amplification corresponding with an increased dependency upon FGF19/FGFR4 autocrine signaling in head and neck squamous cell carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabete  
    FGF19 may serve as an ideal complement for FGF21 in diabetes therapy development
    obesity  
    potential therapeutic candidate for treating diabetes and obesity
    cancerlung 
    FGF19 genetic amplification is a potential therapeutic target in lung squamous cell carcinomas
    cancerdigestiveliver
    FGF19 might be a potential preventive target in hepatocellular carcinoma patients
    neurosensorialvisualretina
    induces dose- and time-dependent phosphorylation of FGFR-4, up-regulates the expression of specific transcription factors, improves survival, and may, hence, represent a useful therapeutic approach to treating retinal degeneration
    ANIMAL & CELL MODELS