Protein Domain : Fibroblast growth factor 15/19/21 IPR035444

Type	Family
Description	This entry includes fibroblast growth factor 15/19/21 (FGF15/19/21).Fibroblast growth factor 15 (FGF15) plays a key role in enterohepatic signaling, regulation of liver bile acid biosynthesis, gallbladder motility and metabolic homeostasis [ , , ]. Mouse FGF15 has been shown to be stimulated when bile acids bind to farnesoid X receptor (FXR) [], and is therefore thought to a factor in chronic bile acid diarrhoea and in certain metabolic disorders [].FGF15 has been experimentally characterised in mouse, but has not been found in other species. However, there is an orthologous human protein, FGF19, and together they share about 50% amino acid identity and display similar endocrine functions, so are often referred to as FGF15/19 [ , ]. FGF15 and FGF19 differ from other FGFs due to subtle changes in their tertiary structure, they have low heparin binding affinity enabling them to diffuse away from their site of secretion and signal to distant cells. FGF signaling through the FGF receptors is also different, as they require klotho protein cofactors rather than heparin sulfate proteoglycan [].Fibroblast growth factor 19 (FGF19) plays a key role in enterohepatic signaling, regulation of liver bile acid biosynthesis, gallbladder motility and metabolic homeostasis [ , , ]. Human FGF19 expression has been shown to be stimulated approximately 300-fold by physiological concentrations of bile acids including chenodeoxycholic acid, glycochenodeoxycholic acid and obeticholic acid in explants of ileal mucosa []. The protein is thought to be a factor in chronic bile acid diarrhoea and in certain metabolic disorders [, ]. FGF19 has been experimentally characterised in humans and other species, but has not been found in mouse. However there is an orthologous mouse protein, FGF15, and together they share about 50% amino acid identity and display similar endocrine functions, so are often referred to as FGF15/19 [, ]. FGF15 and FGF19 differ from other FGFs due to subtle changes in their tertiary structure. They have low heparin binding affinity, enabling them to diffuse away from their site of secretion and signal to distant cells. FGF signaling through the FGF receptors is also different, as they require klotho protein cofactors rather than heparin sulfate proteoglycan []. Unlike other members of the family that can bind several FGF receptors, FGF19 is specific for FGFR4 [].FGF21 stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression [ ]. FGF21 has been shown to protect animals from diet-induced obesity when overexpressed in transgenic mice. It also lowers blood glucose and triglyceride levels when administered to diabetic rodents [], suggesting it may exhibit the therapeutic characteristics necessary for effective treatment of diabetes. Treatment of animals with FGF21 results in increased energy expenditure, fat utilisation and lipid excretion []. FGF21 is most abundantly expressed in the liver, and also expressed in the thymus at lower levels [].
Short Name	FGF15/19/21