FLT3 (fms related receptor tyrosine kinase 3)

Gene

• Entrez ID: 2322
• Gene name: Fms related receptor tyrosine kinase 3
• Gene symbol: FLT3
• Synonyms: CD135, FLK-2, FLK2, STK1
• Chromosome: 13
• Chromosome location: 13q12.2
• Summary: This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121909646	T>A,G	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs121913232	G>C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs121913486	ATC>-	Pathogenic-likely-pathogenic	Inframe deletion, non coding transcript variant, coding sequence variant
rs121913487	A>C,T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs121913488	C>A,G,T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs121913490	GAT>-	Likely-pathogenic	Inframe deletion, non coding transcript variant, coding sequence variant
rs121913491	T>C	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs376588714	T>C	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs398122514	->TCCGGA	Pathogenic	Coding sequence variant, non coding transcript variant, inframe insertion
rs587776834	TCA>-	Pathogenic	Non coding transcript variant, inframe deletion, coding sequence variant
rs749281035	G>A,T	Likely-pathogenic	Non coding transcript variant, synonymous variant, missense variant, coding sequence variant
rs772061268	T>G	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs864321619	->CATATTCTCTGAAATCAACGT	Pathogenic	Inframe insertion, coding sequence variant, non coding transcript variant
rs991132188	T>C	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519726	T>A,C,G	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519762	A>G	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519763	TC>AA	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519764	A>C,T	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519765	T>A,C	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519766	G>C,T	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519767	T>C	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519768	T>C	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057519769	C>A	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057520021	A>C,G	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057520022	A>G	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057520023	A>C	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057520024	T>C	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057520025	A>G	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057520026	T>G	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057520043	A>C	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1208575764	A>G	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1555256794	G>-	Drug-response	5 prime UTR variant, frameshift variant, coding sequence variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT007053	hsa-miR-150-5p	Luciferase reporter assay	23079661
MIRT017462	hsa-miR-335-5p	Microarray	18185580

Transcription factors

Transcription factor	Regulation	Reference
PML	Activation	17124055
STAT3	Activation	16418395

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0001776	Process	Leukocyte homeostasis	ISS
GO:0002318	Process	Myeloid progenitor cell differentiation	ISS
GO:0002328	Process	Pro-B cell differentiation	ISS
GO:0004714	Function	Transmembrane receptor protein tyrosine kinase activity	IBA	21873635
GO:0004714	Function	Transmembrane receptor protein tyrosine kinase activity	TAS	19549778
GO:0004896	Function	Cytokine receptor activity	ISS
GO:0005021	Function	Vascular endothelial growth factor-activated receptor activity	TAS	8394751
GO:0005515	Function	Protein binding	IPI	16982329, 20098747, 23246379, 23650535, 24525236, 27458164, 28086240
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA
GO:0005788	Component	Endoplasmic reticulum lumen	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0007169	Process	Transmembrane receptor protein tyrosine kinase signaling pathway	IBA	21873635
GO:0007275	Process	Multicellular organism development	IBA	21873635
GO:0008284	Process	Positive regulation of cell population proliferation	TAS	19549778
GO:0010243	Process	Response to organonitrogen compound	IEA
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	TAS	12951584
GO:0016032	Process	Viral process	IEA
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	TAS	19549778
GO:0019221	Process	Cytokine-mediated signaling pathway	IBA	21873635
GO:0019221	Process	Cytokine-mediated signaling pathway	ISS
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019838	Function	Growth factor binding	IBA	21873635
GO:0030097	Process	Hemopoiesis	IDA	7507245
GO:0030183	Process	B cell differentiation	IBA	21873635
GO:0030183	Process	B cell differentiation	ISS
GO:0031100	Process	Animal organ regeneration	IEA
GO:0033674	Process	Positive regulation of kinase activity	IBA	21873635
GO:0035259	Function	Glucocorticoid receptor binding	IEA
GO:0035726	Process	Common myeloid progenitor cell proliferation	ISS
GO:0038084	Process	Vascular endothelial growth factor signaling pathway	IEA
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	TAS	19549778
GO:0042981	Process	Regulation of apoptotic process	TAS	19549778
GO:0043235	Component	Receptor complex	IBA	21873635
GO:0043406	Process	Positive regulation of MAP kinase activity	TAS	19549778
GO:0043410	Process	Positive regulation of MAPK cascade	TAS	19549778
GO:0043552	Process	Positive regulation of phosphatidylinositol 3-kinase activity	TAS	12951584
GO:0043621	Function	Protein self-association	IMP	14759363
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0046651	Process	Lymphocyte proliferation	ISS
GO:0046777	Process	Protein autophosphorylation	TAS	19549778
GO:0071345	Process	Cellular response to cytokine stimulus	ISS
GO:0071345	Process	Cellular response to cytokine stimulus	TAS	19549778
GO:0071385	Process	Cellular response to glucocorticoid stimulus	IEA
GO:0097028	Process	Dendritic cell differentiation	ISS

Other IDs

• MIM: 136351
• HGNC: 3765
• e!Ensembl: ENSG00000122025

Protein

• UniProt ID: P36888
• Protein name: Receptor-type tyrosine-protein kinase FLT3 (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Stem cell tyrosine kinase 1) (STK-1) (CD antigen CD135)
• Protein 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.
• PDB: 1RJB, 3QS7, 3QS9, 4RT7, 4XUF, 5X02, 6IL3, 6JQR
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00047	ig	255 → 345	Immunoglobulin domain	Domain
  PF07714	PK_Tyr_Ser-Thr	610 → 943	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKSSSYPMVSESP
  EDLGCALRPQSSGTVYEAAAVEVDVSASITLQVLVDAPGNISCLWVFKHSSLNCQPHFDL
  QNRGVVSMVILKMTETQAGEYLLFIQSEATNYTILFTVSIRNTLLYTLRRPYFRKMENQD
  ALVCISESVPEPIVEWVLCDSQGESCKEESPAVVKKEEKVLHELFGTDIRCCARNELGRE
  CTRLFTIDLNQTPQTTLPQLFLKVGEPLWIRCKAVHVNHGFGLTWELENKALEEGNYFEM
  STYSTNRTMIRILFAFVSSVARNDTGYYTCSSSKHPSQSALVTIVEKGFINATNSSEDYE
  IDQYEEFCFSVRFKAYPQIRCTWTFSRKSFPCEQKGLDNGYSISKFCNHKHQPGEYIFHA
  ENDDAQFTKMFTLNIRRKPQVLAEASASQASCFSDGYPLPSWTWKKCSDKSPNCTEEITE
  GVWNRKANRKVFGQWVSSSTLNMSEAIKGFLVKCCAYNSLGTSCETILLNSPGPFPFIQD
  NISFYATIGVCLLFIVVLTLLICHKYKKQFRYESQLQMVQVTGSSDNEYFYVDFREYEYD
  LKWEFPRENLEFGKVLGSGAFGKVMNATAYGISKTGVSIQVAVKMLKEKADSSEREALMS
  ELKMMTQLGSHENIVNLLGACTLSGPIYLIFEYCCYGDLLNYLRSKREKFHRTWTEIFKE
  HNFSFYPTFQSHPNSSMPGSREVQIHPDSDQISGLHGNSFHSEDEIEYENQKRLEEEEDL
  NVLTFEDLLCFAYQVAKGMEFLEFKSCVHRDLAARNVLVTHGKVVKICDFGLARDIMSDS
  NYVVRGNARLPVKWMAPESLFEGIYTIKSDVWSYGILLWEIFSLGVNPYPGIPVDANFYK
  LIQNGFKMDQPFYATEEIYIIMQSCWAFDSRKRPSFPNLTSFLGCQLADAEEAMYQNVDG
  RVSECPHTYQNRRPFSREMDLGLLSPQAQVEDS

• Sequence length: 993