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

FLT1 (P17948) - Overview - Molecular Target Synopsis

Protein


FLT1, Vascular endothelial growth factor receptor 1
Enzyme Classification 2.7.10.1
UniProt P17948

Also Known as VGFR1_HUMAN, FLT1, FLT, FRT, VEGFR1

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. Interacts with VEGFA, VEGFB and PGF. Monomer in the absence of bound VEGFA, VEGFB or PGF. Homodimer in the presence of bound VEGFA, VEGFB and PGF. Can also form a heterodimer with KDR. Interacts (when tyrosine phosphorylated) with CBL, CRK, GRB2, NCK1, PIK3R1, PLCG, PSEN1 and PTPN11. Probably interacts also with PTPRB. Interacts with RACK1. Identified in a complex with CBL and CD2AP.

5T89
CRYSTAL STRUCTURE OF VEGF-A IN COMPLEX WITH VEGFR-1 DOMAINS D1-6
RCSB/PDB
Inspect Structure
See all 3D Structures for FLT1

Isoforms / Transcripts (Protein Coding)


Drugs


FLT1 is targeted by Approved Drugs Axitinib, Sunitinib, Sorafenib, Pazopanib, Vandetanib. (see details)
Axitinib
Sunitinib
Sorafenib
Pazopanib
Vandetanib

Sub-cellular localization


UniProt: FLT1 is active in the following subcellular-locations: cell membrane, cytoplasm, endosome, secreted.
GO terms: FLT1 is active in the following subcellular-locations: actin cytoskeleton, endosome, extracellular space, focal adhesion, integral component of plasma membrane, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project FLT1 has gain in 4 cell-lines, loss in 5 cell-lines and no signal in 996 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_MEL_2, M14, HS578T

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: WM-115, COLO 857, TYK-nu

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: BJ, HUVEC, HPC-PL

(see details)

RNA Interference


FLT1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB453, SKOV3. (see details)

3D Structures


For FLT1 there are:
12 structures (24 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


FLT1 has been screened with 3148 compounds (5232 bioactivities), 555 compounds have bioactivities that show binding affinity of <= 500nM (750 bioactivities). (see details)