Names & Taxonomy

Uniprot ID:
P22455
Entry Name:
FGFR4_HUMAN
Status:
reviewed
Protein Names:
Fibroblast growth factor receptor 4 (FGFR-4) (EC 2.7.10.1) (CD antigen CD334)
Gene Names:
FGFR4 JTK2 TKF
Gene Names Primary:
FGFR4
Organism:
Homo sapiens (Human)

Structure

Length:
802
Sequence:
MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGSGVQT
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane; Single-pass type I membrane protein. Endosome. Endoplasmic reticulum. Note=Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane.; Isoform 2: Secreted.; Isoform 3: Cytoplasm

Function

Function:
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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
ENZYME REGULATION: Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues.
Active Site:
ACT_SITE 612 612 Proton acceptor.
Cross Reference Drug Bank:
DB09078 DB00039 DB08901
Gene Ontology Go:
cytoplasm
endoplasmic reticulum
endosome
extracellular region
Golgi apparatus
integral component of plasma membrane
nucleoplasm
plasma membrane
transport vesicle
ATP binding
fibroblast growth factor binding
fibroblast growth factor-activated receptor activity
heparin binding
protein tyrosine kinase activity
activation of MAPKK activity
axon guidance
cell migration
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
glucose homeostasis
innate immune response
insulin receptor signaling pathway
MAPK cascade
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine phosphorylation
phosphate ion homeostasis
phosphatidylinositol-mediated signaling
positive regulation of cell proliferation
positive regulation of DNA biosynthetic process
positive regulation of ERK1 and ERK2 cascade
positive regulation of gene expression
positive regulation of metalloenzyme activity
positive regulation of proteolysis
protein autophosphorylation
Ras protein signal transduction
regulation of bile acid biosynthetic process
regulation of cholesterol homeostasis
regulation of extracellular matrix disassembly
regulation of lipid metabolic process
small GTPase mediated signal transduction
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:
activation of MAPKK activity
axon guidance
cell migration
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
glucose homeostasis
innate immune response
insulin receptor signaling pathway
MAPK cascade
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine phosphorylation
phosphate ion homeostasis
phosphatidylinositol-mediated signaling
positive regulation of cell proliferation
positive regulation of DNA biosynthetic process
positive regulation of ERK1 and ERK2 cascade
positive regulation of gene expression
positive regulation of metalloenzyme activity
positive regulation of proteolysis
protein autophosphorylation
Ras protein signal transduction
regulation of bile acid biosynthetic process
regulation of cholesterol homeostasis
regulation of extracellular matrix disassembly
regulation of lipid metabolic process
small GTPase mediated signal transduction
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:
ATP binding
fibroblast growth factor-activated receptor activity
fibroblast growth factor binding
heparin binding
protein tyrosine kinase activity
Gene Ontology Cellular Component:
cytoplasm
endoplasmic reticulum
endosome
extracellular region
Golgi apparatus
integral component of plasma membrane
nucleoplasm
plasma membrane
transport vesicle
Keywords:
3D-structure
ATP-binding
Alternative splicing
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Disulfide bond
Endoplasmic reticulum
Endosome
Glycoprotein
Immunoglobulin domain
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation

Publication

PubMed ID:
1709094 7680645 10631118 9457674 11781352 21882254 15372022 15489334 2247464 15340161 7518429 8663044 11433297 11830541 16597617 17623664 17311277 18756523 18480409 18670643 20638838 20683963 20018895 20798051 21349172 21269460 21412156 21653700 24275569 26675719 17344846 15863030 20094046 20876804