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FLASH GENE

Symbol

FLT3

contributors: mct/npt/pgu - updated : 08-02-2016

HGNC name	fms-related tyrosine kinase 3
HGNC id	3765

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	13q12.2      Physical location : 28.577.411 - 28.674.729
Synonym name	CD135 antigen
	stem cell tyrosine kinase 1
	fetal liver kinase 2
	FLT3 receptor tyrosine kinase
	growth factor receptor tyrosine kinase type III
Synonym symbol(s)	FLK2, STK1, CD135, FLK-2
EC.number	2.7.1.112, 2.7.10.1

DNA

TYPE	functioning gene
SPECIAL FEATURE	arranged in tandem
text	linked in a head to tail configuration with FLT1 and separated by about 150 kb
STRUCTURE	97.32 kb     24 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	cytosine-phosphate-guanine/HTF
text structure	one CpG island

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004119 24 - 3848 NP_004110 - 993 - 2007 18031378

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune thymus         Urinary bladder           kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Homo sapiens Connective bone       Epithelial barrier/lining

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic progenitor cell Homo sapiens Cardiovascular endothelial cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

liver

PROTEIN

PHYSICAL PROPERTIES		Hydrophilic
STRUCTURE

motifs/domains	five immunoglobulin-like C2-type domains in the extracellular region
	a signal peptide domain
	a catalytic domain interrupted in two part by a specific hydrophilic "interkinase" sequence
	a juxtamembrane domain (in ETV6/FLT3 fusion protein is critical for cell proliferation and PIM1 up-regulation that might be independent of a requirement for signaling through STAT5, MAPK, and AKT pathways)

conjugated

GlycoP , PhosphoP

mono polymer

homomer , dimer

HOMOLOGY

interspecies	homolog to murine Flt3
	homolog to C.elegans F59F3.5

Homologene

FAMILY	protein kinase superfamily
	Tyr protein kinase family
	CSF-1/PDGF receptor subfamily

CATEGORY

enzyme , protooncogene , receptor membrane tyrosine kinase

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,lumen
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	type I membrane protein, localized primarily at the cell surface (

basic FUNCTION	receptor for the FL cytokine
	having tyrosine-protein kinase activity
	involved in proliferative events of hematopoietic stem cells
	activated at the late stages of liver regeneration and participates in the proliferation response that is observed during progenitor-dependent liver regeneration
	plays a critical role in maintenance of hematopoietic homeostasis
	FLT3 signaling might play an important role in cell survival, especially at stem and progenitor cells that are critical cellular targets for acute myelogenous leukemia transformation
	FLT3-mediated MAPK14 activation participates in the control of megakaryopoiesis in primary myelofibrosis
	HOXA9 and FLT3 signaling are individually important for the generation of lymphoid lineage precursors from multipotent hematopoietic progenitors (MPP) in bone marrow
	FLT3 signaling plays a crucial role in regulating the survival and differentiation of lymphoid progenitors into B cell precursors (BCPs) in bone marrow
	regulates the proliferation, survival, and maintenance of developmental stage-specific hematopoietic progenitors that give rise to BCPs
	FYN cooperates with oncogenic FLT3-ITD (internal tandem duplication) in cellular transformation by selective activation of the STAT5 pathway

CELLULAR PROCESS	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

text	positive control of cell proliferation

PATHWAY

metabolism

signaling

FLT3 signaling regulates the proliferation, survival, and maintenance of multipotent hematopoietic progenitors that generate B cell precursors

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	binding to the FL cytokine
	PTPRJ is negatively regulating FLT3 signaling activity and its loss may contribute to but is not sufficient for leukemogenic cell transformation
	SOCS6 negatively regulates FLT3 activation, the downstream Erk signaling pathway, and cell proliferation
	FLT3-mediated inhibition of hematopoiesis in KMT2A-AFF1-expressing hESCs, which is associated with large transcriptional changes and downregulation of genes involved in hematopoietic system development and function
	SOCS2 negatively regulates FLT3 signaling by blocking activation of Erk 1/2 and STAT5
	direct interaction of PTPRJ with the hematopoietic receptor-tyrosine kinase Fms-like tyrosine kinase-3 (FLT3), and interaction occurs mainly via an enzyme-substrate complex formation triggered by FLT3 ligand stimulation
	BCL11A is required for expression of I7 receptor (IL7RA) and FLT3 in early hematopoietic progenitor cells
	promotes FLT3 receptor activation in acute myeloid leukemia cells
	CBFB is essential for the development of FLT3(+) macrophage-dendritic cell (DC) progenitors in the bone marrow and all DC subsets in the periphery
	HES1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity
	ITD-FLT3 increases cell migration toward CXCL12 by antagonizing the down-regulation of ROCK1 expression

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   amplification     in childhood acute myeloid leukemia tumoral somatic mutation       duplication mutations within the juxtamembrane domain in adult de novo acute myeloid leukemia tumoral somatic mutation       in high hyperdiploid childhood acute lymphoblastic leukemia tumoral somatic mutation       an internal tandem duplication (FLT3/ITD) is associated with poor prognosis in acute myeloid leukemia (AML), interaction with NPM1 mutations identify 3 prognostic groups: good (FLT3/ITD(-)NPM1(+)), intermediate (FLT3/ITD(-)NPM1(-) or FLT3/ITD(+)NPM1(+)), and poor (FLT3/ITD(+)NPM1(-)) constitutional       gain of function activating mutations in FLT3 induce ligand-independent downstream signaling that promotes oncogenesis through pathways involved in proliferation, differentiation, and survival   fusion translocation     ETV6/FLT3 (EF) fusion proteins in a patient with myeloproliferative disorder (MPD) and a t(12;13)(p13;q12) translocation

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   activated FLT3 is a promising molecular target for AML therapies

ANIMAL & CELL MODELS

model of APL-like disease in mice