FGFR4 Blocking Peptide

This gene encodes a member of the fibroblast growth factor receptor (FGFR) family, with its amino acid sequence being highly conserved between members and among divergent species. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist 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 of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds acidic and basic fibroblast growth hormone and plays a role in bone development and maintenance. Mutations in this gene lead to craniosynostosis and multiple types of skeletal dysplasia. Three alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Jul 2009]

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: Protein kinase, TK; Membrane protein, integral; Kinase, protein; Protein kinase, tyrosine (receptor); EC 2.7.10.1; TK group; FGFR family

Chromosomal Location of Human Ortholog: 5q35.2

Cellular Component: cytoplasm; endoplasmic reticulum; endosome; extracellular region; Golgi apparatus; integral to plasma membrane; intercellular junction; nucleoplasm; plasma membrane; transport vesicle

Molecular Function: 1-phosphatidylinositol-3-kinase activity; ATP binding; fibroblast growth factor binding; fibroblast growth factor receptor activity; heparin binding; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; protein binding; protein-tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity

Biological Process: cell migration; fibroblast growth factor receptor signaling pathway; glucose homeostasis; MAPKKK cascade; peptidyl-tyrosine phosphorylation; phosphate ion homeostasis; phosphoinositide phosphorylation; phosphoinositide-mediated signaling; positive regulation of cell proliferation; positive regulation of GTPase activity; positive regulation of proteolysis; protein amino acid autophosphorylation; regulation of lipid metabolic process; regulation of phosphoinositide 3-kinase cascade