spacer
spacer

Search 

DrugBank target: P36888

DrugBank target: P36888 (FLT3_HUMAN)     

Example structure of target: 1rjb

( There are 6 structures corresponding to this UniProt sequence in the PDB. Click the orange, plus icon above for a list. )

Receptor-type tyrosine-protein kinase FLT3

FL cytokine receptor, Fetal liver kinase-2, Fms-like tyrosine kinase 3, Stem cell tyrosine kinase 1, FLK-2, FLT-3, STK-1.

Function

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..

Enzyme

2.7.10.1   [EC->PDB]   [IntEnz]   [ExPASy]   [KEGG]  

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Disease(s)

Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. Note=The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.

Schematic diagram of Pfam domains in target sequence plus wiring diagrams of PDB structures of target.

1rjb
3qs7
3qs9
1rjb
   more ...

Key:    PfamA domain

Sequence length: 992 a.a.

Approved drugs targeting this protein

The DrugBank database identifies 3 drugs for this target protein:

 

Generic name: DB08901 ponatinib
0LI
Formula: C29H27F3N6O
Structure: There are 4 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB00398 sorafenib
BAX
Formula: C21H16Clf3N4O3
Structure: There are 6 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB01268 sunitinib
B49
Formula: C22H27Fn4O2
Structure: There are 7 PDB structures containing this molecule although none are bound to the above target protein.

  spacer

spacer