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

FGFR1 (P11362) - Overview - Molecular Target Synopsis

Protein


FGFR1, Fibroblast growth factor receptor 1
Enzyme Classification 2.7.10.1
UniProt P11362

Also Known as FGFR1_HUMAN, FGFR1, BFGFR, CEK, FGFBR, FLG, FLT2, HBGFR

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. 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 phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation. Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF5, FGF6, FGF8, FGF10, FGF19, FGF21, FGF22 and FGF23 (in vitro) (PubMed:1697263, PubMed:1722683, PubMed:8663044, PubMed:9655399, PubMed:12181353, PubMed:16597617, PubMed:17623664). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19, FGF21 and FGF23 (PubMed:19966287). Interacts (phosphorylated on Tyr-766) with PLCG1 (via SH2 domains) (PubMed:1656221, PubMed:1379697, PubMed:21765395). Interacts with FRS2 (PubMed:21765395). Interacts with RPS6KA1 (PubMed:15117958). Interacts (via C-terminus) with NEDD4 (via WW3 domain) (PubMed:21765395). Interacts with KL (By similarity). Interacts with SHB (via SH2 domain) (PubMed:12181353). Interacts with GRB10 (PubMed:10454568). Interacts with ANOS1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2 (PubMed:19696444). Interacts with SOX2 and SOX3. Interacts with FLRT1, FLRT2 and FLRT3 (By similarity). Found in a ternary complex with FGF1 and ITGAV:ITGB3 (PubMed:20422052, PubMed:18441324).

6C1B
FGFR1 KINASE COMPLEX WITH INHIBITOR SN37118
RCSB/PDB
Inspect Structure
See all 3D Structures for FGFR1

Isoforms / Transcripts (Protein Coding)


Drugs


FGFR1 is targeted by Approved Drugs Pazopanib, Vandetanib. (see details)
Pazopanib
Vandetanib

Sub-cellular localization


UniProt: FGFR1 is active in the following subcellular-locations: cell membrane, cytoplasm, cytoplasmic vesicle, cytosol, nucleus.
GO terms: FGFR1 is active in the following subcellular-locations: cytoplasmic vesicle, cytosol, extracellular region, integral component of membrane, integral component of plasma membrane, nucleolus, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project FGFR1 has gain in 15 cell-lines, loss in 6 cell-lines and no signal in 982 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: A549, SF_539, ACHN

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MDA-MB-134-VI, CAL-120, G-402

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: NHLF, SK-N-SH, BJ

(see details)

RNA Interference


FGFR1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OS25HAL, OE19. (see details)

3D Structures


For FGFR1 there are:
58 structures (114 chains) solved
46 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

FGFR1 is solved in complex with the approved drug(s):

LEV/LENVATINIB (5ZV2_A, 5ZV2_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


FGFR1 has been screened with 2923 compounds (4548 bioactivities), 821 compounds have bioactivities that show binding affinity of <= 500nM (1194 bioactivities). (see details)