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

FLT3 (P36888) - Overview - Molecular Target Synopsis

Protein


FLT3, Receptor-type tyrosine-protein kinase FLT3
Enzyme Classification 2.7.10.1
UniProt P36888

Also Known as FLT3_HUMAN, FLT3, CD135, FLK2, STK1

Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1 following ligand activation (By similarity). Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2. Interacts with RNF115 and RNF126.

6IL3
CRYSTAL STRUCTURE OF THE FLT3 KINASE BOUND TO A SMALL MOLECULE INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for FLT3

Isoforms / Transcripts (Protein Coding)


Drugs


FLT3 is targeted by Approved Drugs Sorafenib, Sunitinib. (see details)
Sorafenib
Sunitinib

Sub-cellular localization


UniProt: FLT3 is active in the following subcellular-locations: endoplasmic reticulum lumen, membrane.
GO terms: FLT3 is active in the following subcellular-locations: cytosol, endoplasmic reticulum, endoplasmic reticulum lumen, integral component of plasma membrane, nucleus, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project FLT3 has gain in 4 cell-lines, loss in 4 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HL_60, NCI_H460, MOLT_4

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MV-4-11, OCI-AML2, SUP-B15

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: CD34-positive mobilized cell, SK-N-SH, NHLF

(see details)

RNA Interference


FLT3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: TOV21G, MIAPACA2. (see details)

3D Structures


For FLT3 there are:
7 structures (14 chains) solved
5 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


FLT3 has been screened with 2964 compounds (5570 bioactivities), 1052 compounds have bioactivities that show binding affinity of <= 500nM (1536 bioactivities). (see details)