Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

FGFR3 (P22607) - Overview - Molecular Target Synopsis

Protein


FGFR3, Fibroblast growth factor receptor 3
Enzyme Classification 2.7.10.1
UniProt P22607

Also Known as FGFR3_HUMAN, FGFR3, JTK4

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. Monomer. Homodimer after ligand binding. Interacts with FGF1, FGF2, FGF4, FGF6; FGF8, FGF9, FGF10, FGF17, FGF18, FGF19, FGF20 and FGF23 (in vitro). Interacts with KLB. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19 and FGF21. Interacts with PIK3R1, PLCG1, SOCS1 and SOCS3. Isoform 3 forms disulfide-linked dimers.

2LZL
FGFR3TM
RCSB/PDB
Inspect Structure
See all 3D Structures for FGFR3

Isoforms / Transcripts (Protein Coding)


Drugs


FGFR3 is targeted by Approved Drugs Pazopanib, Vandetanib. (see details)
Pazopanib
Vandetanib

Sub-cellular localization


UniProt: FGFR3 is active in the following subcellular-locations: cell membrane, cytoplasmic vesicle, endoplasmic reticulum, secreted.
GO terms: FGFR3 is active in the following subcellular-locations: cell surface, endoplasmic reticulum, extracellular region, Golgi apparatus, integral component of plasma membrane, nucleus, plasma membrane, receptor complex, transport vesicle.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project FGFR3 has gain in 0 cell-lines, loss in 4 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: K_562, NCI_H322M, IGROV1

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: KMS-11, OPM-2, KMS-28PE

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: K562, HepG2, SK-N-SH

(see details)

RNA Interference


FGFR3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HS578T, SAOS2. (see details)

3D Structures


For FGFR3 there are:
3 structures (4 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


FGFR3 has been screened with 1602 compounds (2519 bioactivities), 621 compounds have bioactivities that show binding affinity of <= 500nM (732 bioactivities). (see details)