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

FGFR2 (P21802) - Overview - Molecular Target Synopsis

Protein


FGFR2, Fibroblast growth factor receptor 2
Enzyme Classification 2.7.10.1
UniProt P21802

Also Known as FGFR2_HUMAN, FGFR2, BEK, KGFR, KSAM

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, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1. Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in vitro). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Isoform 1 has high affinity for FGF1 and FGF2, but low affinity for FGF7. Isoform 3 has high affinity for FGF1 and FGF7, and has much higher affinity for FGF7 than isoform 1 (in vitro). 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 PLCG1, GRB2 and PAK4. Interacts with FLRT2.

5UI0
CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FGF RECEPTOR 2 HARBORING AN E565A/K659M DOUBLE GAIN-OF-FUNCTION MUTATION
RCSB/PDB
Inspect Structure
See all 3D Structures for FGFR2

Isoforms / Transcripts (Protein Coding)


Drugs


FGFR2 is targeted by Approved Drugs Pazopanib, Vandetanib, Palifermin. (see details)
Pazopanib
Vandetanib
Palifermin

Sub-cellular localization


UniProt: FGFR2 is active in the following subcellular-locations: cell membrane, cytoplasmic vesicle, golgi apparatus, secreted.
GO terms: FGFR2 is active in the following subcellular-locations: cell cortex, cell surface, cytoplasm, cytoplasmic vesicle, excitatory synapse, extracellular region, Golgi apparatus, integral component of membrane, integral component of plasma membrane, intracellular membrane-bounded organelle, membrane, nucleoplasm, nucleus, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project FGFR2 has gain in 6 cell-lines, loss in 0 cell-lines and no signal in 999 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: T47D, SNB_75, OVCAR_4

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H716, MFM-223, KATO III

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: HMEC, H1-hESC, SK-N-SH

(see details)

RNA Interference


FGFR2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OAW42, PEO14. (see details)

3D Structures


For FGFR2 there are:
40 structures (84 chains) solved
23 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


FGFR2 has been screened with 1302 compounds (2084 bioactivities), 308 compounds have bioactivities that show binding affinity of <= 500nM (391 bioactivities). (see details)