FGFR4 mutated N535K

Tyrosine-protein kinase that acts as a 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.

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.

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.

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.

Expressed in gastrointestinal epithelial cells, pancreas, and gastric and pancreatic cancer cell lines.

• Cell membrane
• Single-pass type I membrane protein
• Endosome
• Endoplasmic reticulum
• Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane.
• Isoform 2
• Secreted

CD334, JTK2, TKF, FGFR4, Fibroblast growth factor receptor 4, FGFR-4

• swissprot:P22455

Proteins

Oncology

87954Da