FLT3 Gene
protein-coding GIFtS : 71 GCID: GC13 M028577
fms-related tyrosine kinase 3
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Aliasesfor FLT3 gene
(According to
1 HGNC ,
2 Entrez Gene ,
3 UniProtKB/Swiss-Prot ,
4 UniProtKB/TrEMBL , 5 OMIM , 6 GeneLoc ,
7 Ensembl ,
8 DME ,
9 miRBase ,
and/or 10 fRNAdb )About This Section Aliases Fms-Related Tyrosine Kinase 3 1 2 FL Cytokine Receptor2 3 CD1351 2 3 EC 2.7.10.13 8 FLK21 2 3 Fetal Liver Kinase 22 STK11 2 3 Growth Factor Receptor Tyrosine Kinase Type III2 Fms-Like Tyrosine Kinase 32 3 Receptor-Type Tyrosine-Protein Kinase FLT32 Stem Cell Tyrosine Kinase 12 3 FLT-33 FLK-22 3 Fetal Liver Kinase-23 STK-12 3 EC 2.7.108 CD135 Antigen2 3
Export aliases for FLT3 gene to outside databases Previous GC identifers: GC13M026557 GC13M022557 GC13M027507 GC13M026375 GC13M027475 GC13M009398
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Summariesfor FLT3 gene (According to Entrez Gene ,
Tocris Bioscience ,
Wikipedia's
Gene Wiki ,
PharmGKB ,UniProtKB/Swiss-Prot ,
and/or
UniProtKB/TrEMBL )
About This Section Entrez Gene summary for FLT3 : This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. The receptor consists of an extracellular domain composed of five immunoglobulin-like domains, one transmembrane region, and a cytoplasmic kinase domain split into two parts by a kinase-insert domain. The 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, Jul 2008) UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888 Function : Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulatesdifferentiation, 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 Gene Wiki entry for FLT3 (CD135)
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Genomic Viewsfor FLT3 gene
(According to
GeneLoc and/or
HGNC , and/or
Entrez Gene (NCBI build 37) ,miRBase ,UCSC (hg19) and
Ensembl (release 69) ,
Regulatory elements and Epigenetics data according to
QIAGEN ,
SABiosciences , and/or
SwitchGear Genomics )About This Section RefSeq DNA sequence: NC_000013.10 NC_018924.1 NT_024524.14 Regulatory elements: SABiosciences Regulatory transcription factor binding sites in the FLT3 gene promoter:STAT5B Pax-5 AP-1 ATF-2 GATA-2 C/EBPalpha STAT3 c-Jun NF-kappaB1 Hlf Other transcription factors Search SABiosciences Chromatin IP Primers for FLT3 Epigenetics: QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human mouse rat
Genomic Location: Genomic View : UCSC Golden Path with GeneCards custom track Entrez Gene cytogenetic band: 13q12 Ensembl cytogenetic band: 13q12.2 HGNC cytogenetic band: 13q12 FLT3 Gene in genomic location: bands according to Ensembl, locations according to
Entrez Gene Ensembl GeneLoc information about chromosome 13 GeneLoc Exon Structure
GeneLoc location for GC13M028577: view genomic region
(about GC identifiers )
Start: 28,577,411 bp from pter End:
28,674,729 bp from pter
Size: 97,319 bases Orientation:
minus strand
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Proteinsfor FLT3 gene
(According to
1 UniProtKB ,
HORDE ,
neXtProt ,
Ensembl ,
and/or Reactome ,
Modification sites according to 2 PhosphoSitePlus ,
Specific Peptides from DME ,
Protein expression images according to data from SPIRE MOPED and PaxDb ,
RefSeq according to NCBI ,
PDB rendering according to OCA and/or Proteopedia ,
Recombinant Proteins
from
EMD Millipore ,
R&D Systems ,
GenScript ,
Enzo Life Sciences ,
OriGene ,
Novus Biologicals ,
Sino Biological ,
ProSpec , and/or
Uscn ,
EMD Millipore ,
R&D Systems ,
OriGene ,
GenScript ,
Cell Signaling Technology ,
Enzo Life Sciences , and/or
Uscn ,
Ontologies according to Gene
Ontology Consortium 01 Mar 2013 and
Entrez Gene ,
Antibodies by
EMD Millipore ,
R&D Systems ,
GenScript ,
Cell Signaling Technology ,
OriGene ,
Novus Biologicals ,
Thermo Fisher Scientific ,
Abcam , and/or
Uscn )
About This Section UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888 See
protein sequence )Recommended Name: Size : 993 amino acids; 112903 DaSubunit : Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1following ligand activation (By similarity). Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2
Subcellular location : Membrane; Single-pass type I membrane protein. Endoplasmic reticulum lumen. Note=Constitutivelyactivated mutant forms with internal tandem duplications are less efficiently transported to the cell surface and a significant proportion is retained in an immature form in the endoplasmic reticulum lumen. The activated kinase is rapidly targeted for degradation
Miscellaneous : Can be used as diagnostic tool to establish the exact cause of acute myeloid leukemia, and to determinethe optimal therapy
3 PDB 3D structures from :1RJB (3D) 3QS7 (3D) 3QS9 (3D) Secondary accessions : A0AVG9 B7ZLT7 B7ZLT8 F5H0A0 Q13414Alternative splicing : 2 isoforms : P36888-1 P36888-2 Explore the universe of human proteins at neXtProt for FLT3: NX_P36888 Post-translational modifications:
N-glycosylated, contains complex N-glycans with sialic acid1 Autophosphorylated on several tyrosine residues in response to FLT3LG binding. FLT3LG binding also increases phosphorylation of mutant kinases that are constitutively activated. Dephosphorylated by PTPRJ/DEP-1, PTPN1, PTPN6/SHP-1, and to a lesser degree by PTPN12. Dephosphorylation is important for export from the endoplasmic reticulum and location at the cell membrane1
Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation1
View modification sites using PhosphoSitePlus 2 View neXtProt modification sites for NX_P36888 4/13 DME Specific Peptides for FLT3 (P36888 ) (see all 13 )FLT3 Protein expression data from MOPED and PaxDb : About this image REFSEQ proteins: NP_004110.2 ENSEMBL proteins: ENSP00000241453 ENSP00000370374 ENSP00000370369 ENSP00000438139 Human Recombinant Protein Products: Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view) : About this table
About GeneDecksing FLT3 Antibody Products: Assay Products for FLT3:
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Protein
Domains /for FLT3 gene (According to InterPro , ProtoNet ,
UniProtKB , and/or BLOCKS ,
Sets of similar genes according to GeneDecks )
About This Section About GeneDecksing 5/12 InterPro domains/families (see all 12 ):
Graphical View of Domain Structure for InterPro Entry P36888 ProtoNet protein and cluster: P36888
2 Blocks protein families : IPB003599 IPB008266 UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888 Domain : The juxtamembrane autoregulatory region is important for normal regulation of the kinase activity and formaintaining the kinase in an inactive state in the absence of bound ligand. Upon tyrosine phosphorylation, it mediates interaction with the SH2 domains of numerous signaling partners. In-frame internal tandem duplications (ITDs) result in constitutive activation of the kinase. The activity of the mutant kinase can be stimulated further by FLT3LG binding Similarity : Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamilySimilarity : Contains 1 Ig-like C2-type (immunoglobulin-like) domainSimilarity : Contains 1 protein kinase domain
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Functionfor FLT3 gene
(According to 1 UniProtKB ,
Genatlas ,
LifeMap Discovery™ ,
IUBMB , and/or
2 DME ,
Human phenotypes from GenomeRNAi ,
Animal models from MGI Mar 06 2013,
SABiosciences ,
miRNA Gene Targets from miRTarBase
shRNA from
OriGene ,
RNAi from
EMD Millipore ,
siRNAs from
OriGene ,
QIAGEN ,
microRNA from QIAGEN ,
Gene Editing from DNA2.0 ,
Clones from EMD Millipore ,
OriGene ,
SwitchGear Genomics ,
GenScript ,
Sino Biological ,
DNA2.0 ,
and Vector BioLabs ,
Cell Lines from GenScript ,
LifeMap BioReagents ,
In Situ Hybridization Assays from Advanced Cell Diagnostics ,
Ontologies according to Gene Ontology Consortium 01 Mar 2013 via
Entrez Gene .)
About This Section Function Summary: UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888 Function : Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulatesdifferentiation, 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 Catalytic activity : ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphateEnzyme regulation : Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads todimerization and activation by autophosphorylation
Genatlas biochemistry entry for FLT3 fms-related receptor tyrosine kinase 3,expressed on endothelial cell,duplicated in childhood acute myeloid leukemia with poor prognosis and acute lymphoblastic leukemia but not in myelodysplastic syndrome Enzyme Numbers (IUBMB): EC 2.7.10.1 1 2 EC 2.7.10 2 Clone Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human mouse rat see all 3 )human mouse rat see all 2 )OriGene custom cloning services – gene synthesis, subcloning, mutagenesis,
variant library, vector shuttling GenScript: all cDNA clones in your preferred vector: FLT3 (NM_004119 ) Sino Biological Human cDNA Clone for FLT3 DNA2.0 Custom Codon Optimized Gene
Synthesis Service for FLT3 Vector BioLabs ready-to-use adenovirus/AAV for human , mouse , rat FLT3
In Situ AssayAdvanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FLT3
Gene Ontology (GO): 5/8 molecular function terms (GO ID links to tree view) (see all 8 ): About this table
About GeneDecksing 2 GenomeRNAi human phenotypes for FLT3 :Animal Models: Flt3 tm1Irl for FLT37 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Flt3) :About GeneDecksing
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Pathways & Interactionsfor FLT3 gene
(Pathways according to
EMD Millipore ,
R&D Systems ,
Cell Signaling Technology ,
KEGG ,
PharmGKB ,
BioSystems ,
Reactome ,
Tocris Bioscience ,
GeneGo (Thomson Reuters) ,
QIAGEN ,
and/or UniProtKB ,
Sets of similar genes according to GeneDecks ,
Interaction Networks according to
SABiosciences ,
and/or STRING ,
Interactions according to 1 UniProtKB ,
2 MINT ,
3 I2D , and/or
4 STRING ,
with links to IntAct and
Ensembl ,
Ontologies according to Gene Ontology Consortium 01 Mar 2013 via
Entrez Gene) .
About This Section Unified GeneCards pathways - 5/16 super-pathways (see all 16 ) About this table See pathways by source Super-pathway contained gene-specific pathways 1 GPCR Pathway 2 Rho Family GTPases 3 Nanog in Mammalian ESC Pluripotency 4 Actin Nucleation by ARP-WASP Complex 5 Akt Signaling
Pathway sources See GeneCards unified pathways Show all pathways 1 5/29 (see all 29 )1 1 1 FLT3 4 (Kegg details for FLT3) :About GeneDecksing Interactions: SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for FLT3 STRING Interaction
Network Preview (showing 5 interactants - click image to see 25)5/32 Interacting proteins for FLT3 (P36888 1 , 2 , 3 ENSP00000241453 4 via UniProtKB, MINT, STRING , and/or I2D (see all 32 )About this table Gene Ontology (GO): 5/26 biological process terms (GO ID links to tree view) (see all 26 ): About this table
GO ID Qualified GO term Evidence PubMed IDs GO:0001776 leukocyte homeostasis
ISS -- GO:0002318 myeloid progenitor cell differentiation
ISS -- GO:0002320 lymphoid progenitor cell differentiation
-- -- GO:0002328 pro-B cell differentiation
ISS -- GO:0002572 pro-T cell differentiation
IEA --
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Drugs & Compoundsfor FLT3 gene (Chemical Compounds according to UniProtKB , Enzo Life Sciences ,
EMD Millipore , Tocris Bioscience
HMDB ,
BitterDB , and/or
Novoseek , and Drugs according to
DrugBank ,
Enzo Life Sciences , and/or
PharmGKB , with drugs/clinical trials/news
search links to CenterWatch )
About This Section About GeneDecksing Compounds for FLT3 available from Tocris Bioscience About this table Compound Action
CAS
# SU 5416 VEGFR inhibitor. Also inhibits KIT, RET, MET and FLT3 [204005-46-9] Lestaurtinib JAK2, FLT3 and TrkA inhibitor [111358-88-4] TCS 359 Potent FLT3 inhibitor [301305-73-7]
2 HMDB Compounds for FLT3 About this table 2 DrugBank Compounds for FLT3 About this table 10/40 Novoseek chemical compound relationships for FLT3 gene (see all 40 ) About this table
Compound
-log (P-Val)
Hits
PubMed IDs for Articles with Shared Sentences (# sentences)
pkc 412
91.7
85
17330105 (5), 18071308 (5), 15956279 (4), 15150124 (4) (see all 27 )
lestaurtinib
88.1
22
16868253 (4), 16857985 (2), 20141349 (2), 18341639 (2) (see all 7 )
tyrosine
85.3
556
17851558 (7), 15345597 (4), 9737679 (3), 14726387 (3) (see all 99 )
tandutinib
84.9
24
16902153 (4), 15256420 (3), 15242881 (3), 19625780 (3) (see all 6 )
ag-1296
80.8
21
11455967 (7), 12357354 (2), 17050201 (2), 18509353 (2) (see all 6 )
sunitinib
74.2
28
17889720 (4), 17041096 (3), 17591828 (1), 18192256 (1) (see all 20 )
daniplestim
67.8
1
10781904 (1)
imatinib
67.8
30
18797870 (3), 14976243 (2), 15180525 (2), 11290609 (1) (see all 13 )
sorafenib
67.5
37
17229632 (6), 18230792 (4), 17889720 (4), 17205056 (2) (see all 20 )
su5416
62.1
11
15158089 (5), 12351406 (2), 17169805 (1), 12649163 (1) (see all 5 )
FLT3
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Transcriptsfor FLT3 gene (Secondary structures according to
fRNAdb ,Unigene
(Build 235 Homo sapiens; Mar 10 2013) or GenBank , Entrez Gene ,
DOTS (version 10), and/or
AceView ,
transcript ids from Ensembl
with links to UCSC , GeneLoc ,
alternative splicing isoforms according to ASD and/or
ECgene ,EMD Millipore ,
OriGene ,
QIAGEN ,
shRNA from
OriGene ,
microRNA from QIAGEN ,
OriGene ,
SwitchGear Genomics ,
GenScript ,
DNA2.0 ,
Vector BioLabs ,
Primers from
OriGene ,
SABiosciences , and/or
QIAGEN
)About This Section REFSEQ mRNAs for FLT3 gene: NM_004119.2 Unigene Cluster for FLT3:
Fms-related tyrosine kinase 3 Hs.507590 [show with all ESTs ] Unigene Representative Sequence: NM_004119 5 Ensembl transcripts including schematic representations, and UCSC links where relevant : ENST00000241453 (uc001urw.3 uc010aao.3 uc010tdn.2 ) ENST00000380987 ENST00000469894 ENST00000380982 ENST00000537084 Clone OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human mouse rat see all 3 )human mouse rat see all 2 )OriGene custom cloning services – gene synthesis, subcloning, mutagenesis,
variant library, vector shuttling GenScript: all cDNA clones in your preferred vector: FLT3 (NM_004119 ) DNA2.0 Custom Codon Optimized Gene
Synthesis Service for FLT3 Vector BioLabs ready-to-use adenovirus/AAV for human , mouse , rat FLT3
Additional cDNA sequence: BC126350.1 BC144039.1 BC144040.1 L36162.1 U02687.1 Z26652.1
4 DOTS entries : DT.120782229 DT.104253
DT.75174632 DT.91675080 17 AceView cDNA sequences :
BX279530 BU681356 BC036028 BF589957 U02687 Z26652 NM_004119 AV713950 AW772610 AW059681 L36162 AW057705 AI150354 BI461248 BF170536 BF176247 BF170584 GeneLoc Exon Structure
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Expression for FLT3 gene
(RNA expression data according to
H-InvDB ,
NONCODE ,
miRBase , and
RNAdb ,
Expression images according to data from
BioGPS ,
Illumina Human BodyMap , and
CGAP
SAGE ,
Sets of similar genes according to GeneDecks ,
in vivo and in vitro expression data from LifeMap Discovery™ ,
plus additional links to
Genevestigator , and/or
SOURCE , and/or
BioGPS , and/or
UniProtKB ,SABiosciences ,
Primers from
OriGene ,
SABiosciences , and/or
QIAGEN ,
In Situ Hybridization Assays from Advanced Cell Diagnostics )
About This Section FLT3 expression in normal human tissues (normalized intensities) See probesets specificity/sensitivity at GeneAnnot About this image BioGPS CGAP TAG: AGTGATTCCA
About this image FLT3 expression in embryonic tissues and stem cells About this table See FLT3 Protein Expression from SPIRE MOPED and PaxDB Genevestigator expression for FLT3 SOURCE GeneReport for Unigene cluster: Hs.507590 UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888 Tissue specificity : Detected in bone marrow, in hematopoietic stem cells, in myeloid progenitor cells and ingranulocyte/macrophage progenitor cells (at protein level). Detected in bone marrow, liver, thymus, spleen and lymph node, and at low levels in kidney and pancreas. Highly expressed in T-cell leukemia SABiosciences Expression via Pathway-Focused PCR Arrays including FLT3 : Primer OriGene genome-wide validated SYBR primer pairs in human mouse rat Browse OriGene validated miRNA SYBR primer pairs SABiosciences RT2 qPCR Primer Assay in human mouse rat QIAGEN QuantiTect SYBR Green Assays in human mouse rat QIAGEN QuantiFast Probe-based Assays in human mouse rat In Situ Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FLT3
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Orthologsfor FLT3 gene
(Orthologs according to
1,2 HomoloGene (2 older version, for species not in 1 newer version),
3 euGenes ,
4 SGD
,
5 MGI Mar 06 2013,
with possible further links to
Flybase
and/or
WormBase ,
and/or
6 Ensembl pan taxonomic compara ,
Gene Trees according to Ensembl and
TreeFam )
About This Section Orthologs for FLT3 gene from 4/14 species (see all 14 ) About this table
ENSEMBL Gene Tree for FLT3 (if available)TreeFam Gene Tree for FLT3 (if available)
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Paralogsfor FLT3 gene (Paralogs according to
1 HomoloGene ,2 Ensembl , and 3 SIMAP , Pseudogenes according to 4 Pseudogene.org Build 68)About This Section Paralogs for FLT3 gene FLT4 2 FGFR4 2 PDGFRB 2 CSF1R 2 FGFR3 2 KIT 2 PDGFRA 2 RET 2 KDR 2 FGFR1 2 FGFR2 2 FLT1 2 17 SIMAP similar genes for FLT3 using alignment to 3 protein entries: FLT3_HUMAN (see all proteins ):STK-1 RET NIN/PDGFRB fusion ABL1 KIT FES CSF1R FGR urf-ret EPHA2 DKFZp686M05208 CDK4 FGFR2 tec PDGFRA TIE1 FGFR3 About GeneDecksing
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Genomic Variantsfor FLT3 gene (SNPs/Variants according to the
1 NCBI SNP Database ,
2 Ensembl ,
3 PupaSUITE ,
UniProtKB , and
DNA2.0 ,
Linkage Disequilibrium by HapMap ,
Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants , Mutations from the Human Gene
Mutation Database (HGMD) and the Locus Specific Mutation
Databases (LSDB) , Blood group antigen gene mutations by BGMUT ,
Resequencing Primers from QIAGEN ,
Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences )
About This Section Genomic Data Transcription Related Data Allele Frequencies SNP ID Valid Clinical Chr 13 pos Sequence # AA Type More # Allele Pop Total More
and Proteopedia 
for FLT3:
GeneGo (Thomson Reuters) Pathway for FLT3
PharmGKB Pathway for 
Kegg Pathways 
Compounds for 
Expression by the Database of Embryonic development, Stem cell research, and
Regenerative medicine 
Anatomical Compartment 
Microarrays
In-situ hybridization