Names & Taxonomy

Uniprot ID:
P22607
Entry Name:
FGFR3_HUMAN
Status:
reviewed
Protein Names:
Fibroblast growth factor receptor 3 (FGFR-3) (EC 2.7.10.1) (CD antigen CD333)
Gene Names:
FGFR3 JTK4
Gene Names Primary:
FGFR3
Organism:
Homo sapiens (Human)

Structure

Length:
806
Sequence:
MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLTQRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAGNPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLPAEEELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCRLRSPPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEGPTLANVSELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPPAPPSSGGSRT
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Isoform 1: Cell membrane; Single-pass type I membrane protein. Cytoplasmic vesicle. Endoplasmic reticulum. Note=The activated receptor is rapidly internalized and degraded. Detected in intracellular vesicles after internalization of the autophosphorylated receptor.; Isoform 2: Cell membrane

Function

Function:
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.
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. Inhibited by SU5402.
Active Site:
ACT_SITE 617 617 Proton acceptor.
Cross Reference Drug Bank:
DB09078 DB09079 DB00039 DB06589 DB08901
Gene Ontology Go:
cell surface
endoplasmic reticulum
extracellular region
Golgi apparatus
integral component of plasma membrane
nucleus
plasma membrane
transport vesicle
ATP binding
fibroblast growth factor binding
fibroblast growth factor-activated receptor activity
protein tyrosine kinase activity
activation of MAPKK activity
axon guidance
bone maturation
bone mineralization
bone morphogenesis
cell-cell signaling
chondrocyte differentiation
chondrocyte proliferation
endochondral bone growth
endochondral ossification
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor apoptotic signaling pathway
fibroblast growth factor receptor signaling pathway
innate immune response
insulin receptor signaling pathway
JAK-STAT cascade
MAPK cascade
negative regulation of developmental growth
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine phosphorylation
phosphatidylinositol-mediated signaling
positive regulation of cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of MAPK cascade
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of phospholipase activity
positive regulation of tyrosine phosphorylation of Stat1 protein
positive regulation of tyrosine phosphorylation of Stat3 protein
protein autophosphorylation
Ras protein signal transduction
skeletal system development
small GTPase mediated signal transduction
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:
activation of MAPKK activity
axon guidance
bone maturation
bone mineralization
bone morphogenesis
cell-cell signaling
chondrocyte differentiation
chondrocyte proliferation
endochondral bone growth
endochondral ossification
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor apoptotic signaling pathway
fibroblast growth factor receptor signaling pathway
innate immune response
insulin receptor signaling pathway
JAK-STAT cascade
MAPK cascade
negative regulation of developmental growth
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine phosphorylation
phosphatidylinositol-mediated signaling
positive regulation of cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of MAPK cascade
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of phospholipase activity
positive regulation of tyrosine phosphorylation of Stat1 protein
positive regulation of tyrosine phosphorylation of Stat3 protein
protein autophosphorylation
Ras protein signal transduction
skeletal system development
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
protein tyrosine kinase activity
Gene Ontology Cellular Component:
cell surface
endoplasmic reticulum
extracellular region
Golgi apparatus
integral component of plasma membrane
nucleus
plasma membrane
transport vesicle
Keywords:
3D-structure
ATP-binding
Alternative splicing
Apoptosis
Cell membrane
Chromosomal rearrangement
Complete proteome
Craniosynostosis
Cytoplasmic vesicle
Deafness
Disease mutation
Disulfide bond
Dwarfism
Ectodermal dysplasia
Endoplasmic reticulum
Glycoprotein
Immunoglobulin domain
Kinase
Lacrimo-auriculo-dento-digital syndrome
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
P05230; P08238

Publication

PubMed ID:
1847508 11703096 15815621 1664411 2247464 7923141 7495869 8663044 10053006 10611230 11294897 12297284 14534538 16597617 16410555 17561467 17509076 17145761 17623664 17311277 19088846 18669648 19286672 15863030 15748888 19066716 20094046 14732692 8078586 7847369 7758520 8589699 7773297 7670477 7493034 8599935 8845844 8754806 9042914 9207791 9790257 10215410 9452043 10671061 9525367 10360402 9950359 10471491 11055896 10777366 11746040 11529856 11325814 11314002 12707965 15772091 17033969 16841094 16501574 17935505 17344846 19855393