FGFR4 - Fibroblast growth factor receptor 4 - human protein (Function)
 
Home Recent activites arrow-down favorite My favorites arrow-down favorite My labels arrow-down Downloads
Back to ...  
Publication View
Protein
Gene
References

 
FGFR4 »  Fibroblast growth factor receptor 4   [ EC 2.7.10.1 ]  (FGFR-4)
 
Protein also known as:  CD antigen CD334.
Gene name:  FGFR4
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 133 3
GENE REF ISO

Function

 show evidences
Overview 
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.  
14
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Fibroblast growth factor bindingdefinition[GO:0017134]  
3
  • IDAUniProtKB
Fibroblast growth factor-activated receptor activitydefinition[GO:0005007]  
4
  • IDAUniProtKB
  • IGIMGI
Heparin bindingdefinition[GO:0008201]  
1
  • IDAUniProtKB
GO biological process 
Alveolar secondary septum developmentdefinition[GO:0061144] silver  
  • IEAOrtholog Compara
Cell migrationdefinition[GO:0016477]  
1
  • IMPUniProtKB
Fibroblast growth factor receptor signaling pathwaydefinition[GO:0008543]  
3
  • IDAUniProtKB
  • IPIMGI
Glucose homeostasisdefinition[GO:0042593]  
  • ISSOrtholog Curator
Organ inductiondefinition[GO:0001759] silver  
  • IEAOrtholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
2
  • IDAUniProtKB
Phosphate ion homeostasisdefinition[GO:0055062]  
  • ISSOrtholog Curator
Positive regulation of cell proliferationdefinition[GO:0008284]  
2
  • IDAUniProtKB
  • IGIMGI
Positive regulation of DNA biosynthetic processdefinition[GO:2000573]  
1
  • IMPUniProtKB
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • IMPUniProtKB
Positive regulation of metalloenzyme activitydefinition[GO:0048554]  
1
  • IMPUniProtKB
Positive regulation of proteolysisdefinition[GO:0045862]  
1
  • IMPUniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAUniProtKB
Regulation of bile acid biosynthetic processdefinition[GO:0070857]  
2
  • IMPUniProtKB
Regulation of cholesterol homeostasisdefinition[GO:2000188]  
  • ISSOrtholog Curator
Regulation of extracellular matrix disassemblydefinition[GO:0010715]  
1
  • IMPUniProtKB
Regulation of lipid metabolic processdefinition[GO:0019216]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
4
  • CuratedUniProtKB
It is regulated in the following manner
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues.  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Endocytosis  hsa04144+2264  
MAPK signaling pathway  hsa04010+2264  
Regulation of actin cytoskeleton  hsa04810+2264  
According to Reactome, this protein belongs to the following pathways:
betaKlotho-mediated ligand binding  REACT_111046  
Constitutive PI3K/AKT Signaling in Cancer  REACT_147727  
FGFR4 ligand binding and activation  REACT_9452  
FRS2-mediated cascade  REACT_21247  
Negative regulation of FGFR signaling  REACT_111184  
Phospholipase C-mediated cascade  REACT_21310  
PI-3K cascade  REACT_21270  
PI3K Cascade  REACT_976  
PIP3 activates AKT signaling  REACT_75829  
SHC-mediated cascade  REACT_21374  
Signaling by FGFR mutants  REACT_121398  
Signaling by FGFR4 mutants  REACT_121286  
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Fibroblast_growth_factor_receptor_4
GenomeRNAi: 2264
PRO: PR:P22455
Chemistry
GuidetoPHARMACOLOGY: 1811