Fibroblast growth factor 19
PDB rendering based on 1pwa.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1PWA, 2P23
Identifiers
Symbol	FGF19
External IDs	OMIM: 603891 MGI: 1096383 HomoloGene: 3754 GeneCards: FGF19 Gene
Gene Ontology Molecular function • fibroblast growth factor receptor binding • protein binding • growth factor activity Cellular component • extracellular region Biological process • neural crest cell migration • epidermal growth factor receptor signaling pathway • nervous system development • heart development • positive regulation of cell proliferation • insulin receptor signaling pathway • fibroblast growth factor receptor signaling pathway • innate immune response • positive regulation of glucose import • positive regulation of JNK cascade • neurotrophin TRK receptor signaling pathway • phosphatidylinositol-mediated signaling • positive regulation of ERK1 and ERK2 cascade • negative regulation of bile acid biosynthetic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9965	14170
Ensembl	ENSG00000162344	ENSMUSG00000031073
UniProt	O95750	O35622
RefSeq (mRNA)	NM_005117	NM_008003
RefSeq (protein)	NP_005108	NP_032029
Location (UCSC)	Chr 11: 69.51 – 69.52 Mb	Chr 7: 144.9 – 144.9 Mb
PubMed search	[1]	[2]
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Fibroblast growth factor 19 is a protein that in humans is encoded by the FGF19 gene.^[1] It functions as a hormone, regulating bile acid synthesis, with effects on glucose and lipid metabolism.^[2][3]

Functions [edit]

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes including embryonic development cell growth, morphogenesis, tissue repair, tumor growth and invasion. This growth factor is a high affinity, heparin dependent ligand for FGFR4.^[4] Expression of this gene was detected only in fetal but not adult brain tissue.^[5] Synergistic interaction of the chick homolog and Wnt-8c has been shown to be required for initiation of inner ear development.^[1][6][7]

The orthologous protein in mouse is FGF15, which shares about 50% amino acid identity and has similar functions. Together they are often referred to as FGF15/19.^[2][3]

FGF19 has important roles as a hormone produced in the ileum in response to bile acid absorption.^[3] Bile acids bind to the farnesoid X receptor (FXR), stimulating FGF19 transcription and several FXR / bile acid response elements have been identified in the FGF19 gene.^[8]

FGF19 regulates new bile acid synthesis, acting through the FGFR4/Klotho-β receptor complexes in the liver to inhibit CYP7A1.^{[9][10][11][12]}

FGF19 also has metabolic effects, affecting glucose and lipid metabolism when used in experimental mouse models.^[13][14][15]

Clinical significance [edit]

Patients with chronic diarrhea due to bile acid malabsorption have been shown to have reduced fasting FGF19.^[16] Surgical resection of the ileum (as often occurs in Crohn's disease) will reduce bile acid absorption and remove the stimulus for FGF19 production. In primary bile acid diarrhea, absorption of bile acids is usually normal, but defective FGF19 production can produce excessive bile acid synthesis, as shown by increased levels of 7α-hydroxy-4-cholesten-3-one.^[17]

FGF19 is also found in the liver of patients with cholestasis.^[18] It can be synthesised in the gall-bladder and secreted into bile.^[19]

Patients with the metabolic syndrome, non-alcoholic fatty liver disease and insulin resistance have reduced levels of FGF19.^[20][21] FGF19 increases to normal values in obese patients who undergo Roux-en-Y gastric bypass bariatric surgery.^[22]

References [edit]

Further reading [edit]

v t e PDB gallery 1pwa: Crystal structure of Fibroblast Growth Factor 19  2p23: Crystal structure of human FGF19