FGFR4

The protein encoded by this gene is a tyrosine kinase and cell surface receptor for fibroblast growth factors. The encoded protein is involved in the regulation of several pathways, including cell proliferation, cell differentiation, cell migration, lipid metabolism, bile acid biosynthesis, vitamin D metabolism, glucose uptake, and phosphate homeostasis. This protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment, and a cytoplasmic tyrosine kinase domain. The extracellular portion interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. [provided by RefSeq, Aug 2017]

Fibroblast Growth Factor Receptor 4

Tyrosine-protein kinase 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 RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. 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.

Cell migration Source: UniProtKB
Cholesterol homeostasis Source: UniProtKB
Fibroblast growth factor receptor signaling pathway Source: UniProtKB
Glucose homeostasis Source: UniProtKB
Peptidyl-tyrosine phosphorylation Source: UniProtKB
Phosphate ion homeostasis Source: UniProtKB
Positive regulation of catalytic activity Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of DNA biosynthetic process Source: UniProtKB
Positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Positive regulation of gene expression Source: UniProtKB
Positive regulation of kinase activity Source: GO_Central
Positive regulation of proteolysis Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Regulation of bile acid biosynthetic process Source: UniProtKB
Regulation of extracellular matrix disassembly Source: UniProtKB
Regulation of lipid metabolic process Source: UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central

Endoplasmic reticulum; Endosome; Cell membrane. Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane.
Isoform 2: Secreted
Isoform 3: Cytoplasm

FGFR4 variants may be involved in the pathogenesis of various cancers. Variant Arg-388 predisposes cancer patients to accelerated disease progression and may be associated with poor prognosis. It has been found in prostate cancer as well as cancers of the breast, colon, head and neck, larynx, lung, skin.

Extracellular: 22-369
Helical: 370-390
Cytoplasmic: 391-802

N-glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19.
Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated.
Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer.