FGFR3 - Fibroblast growth factor receptor 3 - human protein (Function)
 
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FGFR3 »  Fibroblast growth factor receptor 3   [ EC 2.7.10.1 ]  (FGFR-3)
 
Protein also known as:  CD antigen CD333.
Gene name:  FGFR3
Entry whose protein(s) existence is based on evidence at protein level
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1 356 4
GENE REF ISO

Function

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Overview 
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL 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. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling.  
14
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Fibroblast growth factor bindingdefinition[GO:0017134]  
2
  • MGI
  • UniProtKB
Fibroblast growth factor-activated receptor activitydefinition[GO:0005007]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
2
  • IntAct
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • UniProtKB
GO biological process 
Alveolar secondary septum developmentdefinition[GO:0061144] silver  
1
  • Ortholog Compara
Axonogenesis involved in innervationdefinition[GO:0060385] silver  
1
  • Ortholog Compara
Bone maturationdefinition[GO:0070977]  
1
  • BHF-UCL
Bone mineralizationdefinition[GO:0030282]  
1
  • BHF-UCL
Bone morphogenesisdefinition[GO:0060349]  
2
  • BHF-UCL
  • UniProtKB
Cell-cell signalingdefinition[GO:0007267] silver  
1
  • Ortholog Compara
Central nervous system myelinationdefinition[GO:0022010] silver  
1
  • Ortholog Compara
Chondrocyte differentiationdefinition[GO:0002062]  
1
  • UniProtKB
Chondrocyte proliferationdefinition[GO:0035988]  
1
  • UniProtKB
Cochlea developmentdefinition[GO:0090102] silver  
1
  • Ortholog Compara
Digestive tract morphogenesisdefinition[GO:0048546] silver  
1
  • Ortholog Compara
Endochondral bone growthdefinition[GO:0003416]  
1
  • UniProtKB
Endochondral ossificationdefinition[GO:0001958]  
1
  • UniProtKB
Epithelial cell fate commitmentdefinition[GO:0072148] silver  
1
  • Ortholog Compara
Fibroblast growth factor receptor apoptotic signaling pathwaydefinition[GO:1902178]  
1
  • UniProtKB
Fibroblast growth factor receptor signaling pathwaydefinition[GO:0008543]  
2
  • MGI
  • UniProtKB
Forebrain developmentdefinition[GO:0030900] silver  
1
  • Ortholog Compara
Inner ear receptor cell differentiationdefinition[GO:0060113] silver  
1
  • Ortholog Compara
JAK-STAT cascadedefinition[GO:0007259]  
1
  • PINC
Lens fiber cell developmentdefinition[GO:0070307] silver  
1
  • Ortholog Compara
Lens morphogenesis in camera-type eyedefinition[GO:0002089] silver  
1
  • Ortholog Compara
MAPK cascadedefinition[GO:0000165] silver  
1
  • Ortholog Compara
Morphogenesis of an epitheliumdefinition[GO:0002009] silver  
1
  • Ortholog Compara
Negative regulation of astrocyte differentiationdefinition[GO:0048712] silver  
1
  • Ortholog Compara
Negative regulation of developmental growthdefinition[GO:0048640]  
1
  • BHF-UCL
Negative regulation of epithelial cell proliferationdefinition[GO:0050680] silver  
1
  • Ortholog Compara
Negative regulation of mitotic nuclear divisiondefinition[GO:0045839] silver  
1
  • Ortholog Compara
Negative regulation of smoothened signaling pathwaydefinition[GO:0045879] silver  
1
  • Ortholog Compara
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • UniProtKB
Positive regulation of canonical Wnt signaling pathwaydefinition[GO:0090263] silver  
1
  • Ortholog Compara
Positive regulation of cell differentiationdefinition[GO:0045597] silver  
1
  • Ortholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284]  
3
  • UniProtKB
  • MGI
Positive regulation of endothelial cell proliferationdefinition[GO:0001938] silver  
1
  • Ortholog Compara
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • UniProtKB
Positive regulation of MAPK cascadedefinition[GO:0043410]  
1
  • UniProtKB
Positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathwaydefinition[GO:0090080] silver  
1
  • Ortholog Compara
Positive regulation of neuron apoptotic processdefinition[GO:0043525] silver  
1
  • Ortholog Compara
Positive regulation of phosphatidylinositol 3-kinase activitydefinition[GO:0043552]  
2
  • UniProtKB
Positive regulation of phospholipase activitydefinition[GO:0010518]  
1
  • UniProtKB
Positive regulation of protein ubiquitinationdefinition[GO:0031398] silver  
1
  • Ortholog Compara
Positive regulation of tyrosine phosphorylation of Stat1 proteindefinition[GO:0042511]  
2
  • UniProtKB
Positive regulation of tyrosine phosphorylation of Stat3 proteindefinition[GO:0042517]  
1
  • UniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
1
  • UniProtKB
Response to axon injurydefinition[GO:0048678] silver  
1
  • Ortholog Compara
Skeletal system developmentdefinition[GO:0001501]  
1
  • PINC
Somatic stem cell maintenancedefinition[GO:0035019] silver  
1
  • Ortholog Compara
Substantia nigra developmentdefinition[GO:0021762] silver  
1
  • Ortholog Compara
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
  • UniProtKB
  • PROSITE-ProRule
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. Inhibited by SU5402.  
4
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Bladder cancer  hsa05219+2261  
Endocytosis  hsa04144+2261  
MAPK signaling pathway  hsa04010+2261  
Pathways in cancer  hsa05200+2261  
Regulation of actin cytoskeleton  hsa04810+2261  
According to Reactome, this protein belongs to the following pathways:
Constitutive PI3K/AKT Signaling in Cancer  REACT_147727  
FGFR3b ligand binding and activation  REACT_9508  
FGFR3c ligand binding and activation  REACT_9510  
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 activated point mutants of FGFR3  REACT_121337  
Signaling by FGFR mutants  REACT_121398  
Signaling by FGFR3 mutants  REACT_121249  
t(4;14) translocations of FGFR3  REACT_121011  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
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_3
GenomeRNAi: 2261
PRO: PR:P22607
Chemistry
GuidetoPHARMACOLOGY: 1810