the FLT3 gene contains 24 exons and spans 96,982 bases (start:27,475,753 bp to end 27,572,735 from 13pter) oriented at the minus strand.

3.7 kb; 2979 bp open reading frame

Size: 993 amino acids; 112804 Da;
FLT3 is a class III receptor tyrosine kinase (RTK) structurally related to the receptors for platelet derived growth factor (PDGF), colony stimulating factor 1 (CSF1), and KIT ligand (KL).; these RTK contain five immunoglobulin-like domains in the extracellular region and an intracelular tyrosine kinase domain splitted in two by a specific hydrophilic insertion (kinase insert); immunoprecipitation of the human FLT3 protein results in the appearance of a minor band of Mr 130 000 and a major band of Mr 155 000/160 000; the high-molecular-weight band corresponds to the mature, N-glycosylated form, and the low-molecular-weight band to the immature, high mannose-containing form; N-linked glycosylations account for 50 000 daltons.

FLT3 expression was described on bone marrow CD34-positive cells, corresponding to multipotential, myeloid and B-lymphoid progenitor cells, and on monocytic cells; FLT3 expression is restricted to cells of the fetal liver expressing high levels of CD34; in addition, the FLT3 protein is expressed on blast cells from most AML and B-ALL.

Subcellular location: Type I membrane protein. 3D structure: PDB id 1RJB (3D).

FLT3 receptor function can be defined by the activity of its ligand (FL); FL is an early acting factor and supports the survival, proliferation and differentiation of primitive hemopoietic progenitor cells. Ligand binding to FLT3 promotes receptor dimerization and subsequent signalling through posphorylation of multiple cytoplasmatic proteins, including SHC, SHP-2, SHIP, Cbl, Cbl-b, Gab1 and Gab2, as well as the activation of several downstream signalling pathways, such as the Ras/Raf/MAPK and PI3 kinase cascades.
Function: Receptor for the FL cytokine. Has a tyrosine-protein kinase activity. Catalytic activity: ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
Similarity: Belongs to the Tyr protein kinase family. CSF-1/PDGF receptor subfamily. Contains 1 immunoglobulin-like C2-type domain.

Other tyrosine kinases: KIT, PDGFRA, PDGFRB, VEGFR

Mutations in the FLT3 gene are the most frequent genetic aberration that have been described in acute myeloid leukemia. With 20-25% length mutations in the juxtamembrane domain are the most frequent, followed by 7-8% mutations in the second tyrosine kinase kinase domain, mostly point mutations in codon 835 or deletions of codon 836. Also point mutations in the juxta membrane domain have been described and the number of new mutations all over the total gene is still growing.