FGFR4: a tyrosine-kinase receptor that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of the MAP kinase and AKT signaling pathways. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling. Two isoforms of the human protein are formed by alternative splicing. This description may include information from UniProtKB
Protein type: Membrane protein, integral; Kinase, protein; Protein kinase, tyrosine (receptor); Protein kinase, TK; EC 2.7.10.1; TK group; FGFR family
Chromosomal Location of Human Ortholog: 5q35.2
Cellular Component: nucleoplasm; Golgi apparatus; transport vesicle; endoplasmic reticulum; integral to plasma membrane; cytoplasm; extracellular region; plasma membrane; intercellular junction; endosome
Molecular Function: heparin binding; protein binding; fibroblast growth factor binding; fibroblast growth factor receptor activity; protein-tyrosine kinase activity; ATP binding
Biological Process: epidermal growth factor receptor signaling pathway; cell migration; regulation of lipid metabolic process; fibroblast growth factor receptor signaling pathway; peptidyl-tyrosine phosphorylation; phosphoinositide-mediated signaling; nerve growth factor receptor signaling pathway; positive regulation of proteolysis; protein amino acid autophosphorylation; positive regulation of metalloenzyme activity; glucose homeostasis; induction of an organ; positive regulation of cell proliferation; insulin receptor signaling pathway; innate immune response; phosphate ion homeostasis
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