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Aliases for FLT3 Gene

Aliases for FLT3 Gene

  • Fms-Related Tyrosine Kinase 3 2 3
  • Stem Cell Tyrosine Kinase 1 3 4
  • Fms-Like Tyrosine Kinase 3 3 4
  • FL Cytokine Receptor 3 4
  • CD135 Antigen 3 4
  • EC 2.7.10.1 4 64
  • CD135 3 4
  • FLK-2 3 4
  • STK1 3 4
  • FLK2 3 4
  • Growth Factor Receptor Tyrosine Kinase Type III 3
  • Receptor-Type Tyrosine-Protein Kinase FLT3 3
  • Fetal Liver Kinase 2 3
  • Fetal Liver Kinase-2 4
  • EC 2.7.10 64
  • FLT-3 4
  • STK-1 4

External Ids for FLT3 Gene

Summaries for FLT3 Gene

Entrez Gene Summary for FLT3 Gene

  • 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]

GeneCards Summary for FLT3 Gene

FLT3 (Fms-Related Tyrosine Kinase 3) is a Protein Coding gene. Diseases associated with FLT3 include minimally differentiated acute myeloblastic leukemia and lymphoblastic leukemia. Among its related pathways are GPCR Pathway and Pathways in cancer. GO annotations related to this gene include protein homodimerization activity and phosphatidylinositol 3-kinase binding. An important paralog of this gene is FGFR3.

UniProtKB/Swiss-Prot for FLT3 Gene

  • 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.

Tocris Summary for FLT3 Gene

  • FMS-like receptor tyrosine kinase-3 (FLT3) is a member of the class III RTK (receptor tyrosine kinase) family and is expressed primarily in hematopoietic progenitor cells. The expression within these cells demonstrates that FLT3 has an important role in the pathogenesis of AML (acute myelogenous leukemia), under which conditions wild type receptors are overexpressed or mutated forms of the receptor are present. Inhibitors of both mutated and wild type receptors are therefore of interest in a therapeutic context.

Gene Wiki entry for FLT3 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FLT3 Gene

Genomics for FLT3 Gene

Genomic Location for FLT3 Gene

Start:
28,003,274 bp from pter
End:
28,100,592 bp from pter
Size:
97,319 bases
Orientation:
Minus strand

Genomic View for FLT3 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for FLT3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FLT3 Gene

Regulatory Elements for FLT3 Gene

Proteins for FLT3 Gene

  • Protein details for FLT3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P36888-FLT3_HUMAN
    Recommended name:
    Receptor-type tyrosine-protein kinase FLT3
    Protein Accession:
    P36888
    Secondary Accessions:
    • A0AVG9
    • B7ZLT7
    • B7ZLT8
    • F5H0A0
    • Q13414

    Protein attributes for FLT3 Gene

    Size:
    993 amino acids
    Molecular mass:
    112903 Da
    Quaternary structure:
    • Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1 following ligand activation (By similarity). Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2. Interacts with RNF115 and RNF126 (By similarity).
    Miscellaneous:
    • Can be used as diagnostic tool to establish the exact cause of acute myeloid leukemia, and to determine the optimal therapy

    Three dimensional structures from OCA and Proteopedia for FLT3 Gene

    Alternative splice isoforms for FLT3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FLT3 Gene

Proteomics data for FLT3 Gene at MOPED

Post-translational modifications for FLT3 Gene

  • 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 membrane
  • N-glycosylated, contains complex N-glycans with sialic acid.
  • Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys614 and Lys623
  • Glycosylation at Asn43, Asn100, Asn151, Asn306, Asn323, Asn351, Asn354, Asn473, Asn502, and Asn541

Other Protein References for FLT3 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains for FLT3 Gene

Gene Families for FLT3 Gene

UniProtKB/Swiss-Prot:

FLT3_HUMAN
Domain:
  • The juxtamembrane autoregulatory region is important for normal regulation of the kinase activity and for maintaining 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:
    • P36888
  • Contains 1 Ig-like C2-type (immunoglobulin-like) domain.:
    • P36888
  • Contains 1 protein kinase domain.:
    • P36888
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.:
    • P36888
genes like me logo Genes that share domains with FLT3: view

Function for FLT3 Gene

Molecular function for FLT3 Gene

GENATLAS Biochemistry: 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
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation: Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation.
UniProtKB/Swiss-Prot 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 Numbers (IUBMB) for FLT3 Gene

Gene Ontology (GO) - Molecular Function for FLT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity --
GO:0004713 protein tyrosine kinase activity --
GO:0004714 transmembrane receptor protein tyrosine kinase activity TAS 19549778
GO:0004896 cytokine receptor activity ISS --
GO:0005021 vascular endothelial growth factor-activated receptor activity TAS 8394751
genes like me logo Genes that share ontologies with FLT3: view
genes like me logo Genes that share phenotypes with FLT3: view

Animal Models for FLT3 Gene

MGI Knock Outs for FLT3:

miRNA for FLT3 Gene

miRTarBase miRNAs that target FLT3

No data available for Transcription Factor Targeting and HOMER Transcription for FLT3 Gene

Localization for FLT3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FLT3 Gene

Membrane; Single-pass type I membrane protein. Endoplasmic reticulum lumen. Note=Constitutively activated 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.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for FLT3 Gene COMPARTMENTS Subcellular localization image for FLT3 gene
Compartment Confidence
endoplasmic reticulum 5
plasma membrane 4
extracellular 2
nucleus 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for FLT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm --
GO:0005783 endoplasmic reticulum --
GO:0005788 endoplasmic reticulum lumen IEA --
GO:0005829 cytosol IEA --
genes like me logo Genes that share ontologies with FLT3: view

Pathways for FLT3 Gene

genes like me logo Genes that share pathways with FLT3: view

Pathways by source for FLT3 Gene

1 GeneGo (Thomson Reuters Life Sciences Research) pathway for FLT3 Gene
1 Cell Signaling Technology pathway for FLT3 Gene

Gene Ontology (GO) - Biological Process for FLT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001776 leukocyte homeostasis ISS --
GO:0001934 positive regulation of protein phosphorylation --
GO:0002318 myeloid progenitor cell differentiation ISS --
GO:0002320 lymphoid progenitor cell differentiation --
GO:0002328 pro-B cell differentiation ISS --
genes like me logo Genes that share ontologies with FLT3: view

Compounds for FLT3 Gene

(12) ApexBio Compounds for FLT3 Gene

Compound Action Cas Number
Amuvatinib (MP-470, HPK 56) Multi-kinase inhibitor, inhibits PDGFR, c-Kit, and Flt3 [850879-09-3]
AST 487 high selectivity and potency toward FLT3 [630124-46-8]
Cabozantinib (XL184, BMS-907351) Multi-target kinase inhibitor, inhibits c-Met, VEGFR2, and RET [849217-68-1]
KW 2449 multiple-targeted inhibitor, mostly for Flt3. [1000669-72-6]
Lestaurtinib Potent JAK2, FLT3 and TrkA inhibitor. [111358-88-4]
Linifanib (ABT-869) ATP-competitive, multi-targeted RTK inhibitor [796967-16-3]
Ponatinib (AP24534) pan-BCR-ABL inhibitor [943319-70-8]
Quizartinib (AC220) Potent and selective FLT3 inhibitor [950769-58-1]
SB1317 novel pyrimidine-based multi-kinase inhibitor that inhibits CDKs 1, 2, 7 and 9 together with JAK2 and FLT3 [937270-47-8]
SU5416 VEGF receptor inhibitor and an aryl hydrocarbon receptor (AHR) agonist [204005-46-9]
TCS 359 Potent inhibitor of FLT3 receptor tyrosine kinase [301305-73-7]
TG101209 JAK2 and 3 inhibitor, also inhibits Flt3 and RET [936091-14-4]

(2) Tocris Compounds for FLT3 Gene

Compound Action Cas Number
5-Fluoroindirubinoxime FLT3 inhibitor; displays antiproliferative activity [861214-33-7]
TCS 359 Potent FLT3 inhibitor [301305-73-7]

(2) HMDB Compounds for FLT3 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(3) Drugbank Compounds for FLT3 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Ponatinib
943319-70-8 target inhibitor
Sorafenib
284461-73-0 target antagonist
Sunitinib
  • SU011248
557795-19-4 target multitarget

(1) IUPHAR Ligand for FLT3 Gene

Ligand Type Action Affinity Pubmed IDs
Fms-related tyrosine kinase 3 ligand None None

(40) Novoseek inferred chemical compound relationships for FLT3 Gene

Compound -log(P) Hits PubMed IDs
pkc 412 91.7 57
lestaurtinib 88.1 13
tyrosine 85.3 181
tandutinib 84.9 17
ag-1296 80.8 16
genes like me logo Genes that share compounds with FLT3: view

Transcripts for FLT3 Gene

mRNA/cDNA for FLT3 Gene

Unigene Clusters for FLT3 Gene

Fms-related tyrosine kinase 3:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for FLT3 Gene

No ASD Table

Relevant External Links for FLT3 Gene

GeneLoc Exon Structure for
FLT3
ECgene alternative splicing isoforms for
FLT3

Expression for FLT3 Gene

mRNA expression in normal human tissues for FLT3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for FLT3 Gene

This gene is overexpressed in Brain - Cerebellar Hemisphere (11.9), Brain - Cerebellum (10.0), and Whole Blood (8.3).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for FLT3 Gene

SOURCE GeneReport for Unigene cluster for FLT3 Gene Hs.507590

mRNA Expression by UniProt/SwissProt for FLT3 Gene

P36888-FLT3_HUMAN
Tissue specificity: Detected in bone marrow, in hematopoietic stem cells, in myeloid progenitor cells and in granulocyte/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.
genes like me logo Genes that share expressions with FLT3: view

Orthologs for FLT3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for FLT3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FLT3 36
  • 99.6 (n)
  • 98.99 (a)
FLT3 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia FLT3 36
  • 88.27 (n)
  • 90.64 (a)
FLT3 37
  • 90 (a)
OneToOne
dog
(Canis familiaris)
Mammalia FLT3 36
  • 90.74 (n)
  • 91.84 (a)
FLT3 37
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Flt3 36
  • 83.15 (n)
  • 86.18 (a)
Flt3 16
Flt3 37
  • 85 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia FLT3 37
  • 74 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia FLT3 37
  • 64 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Flt3 36
  • 82.31 (n)
  • 84.53 (a)
chicken
(Gallus gallus)
Aves FLT3 36
  • 65.12 (n)
  • 57.13 (a)
FLT3 37
  • 54 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia FLT3 37
  • 52 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia flt3 36
  • 59.73 (n)
  • 51.99 (a)
zebrafish
(Danio rerio)
Actinopterygii flt3 36
  • 53.5 (n)
  • 45.67 (a)
flt3 37
  • 35 (a)
OneToOne
Species with no ortholog for FLT3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for FLT3 Gene

ENSEMBL:
Gene Tree for FLT3 (if available)
TreeFam:
Gene Tree for FLT3 (if available)

Paralogs for FLT3 Gene

Paralogs for FLT3 Gene

Selected SIMAP similar genes for FLT3 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with FLT3: view

Variants for FLT3 Gene

Sequence variations from dbSNP and Humsavar for FLT3 Gene

SNP ID Clin Chr 13 pos Sequence Context AA Info Type MAF
rs1042106 -- 28,003,792(-) CAGGC(C/T)GGCTT utr-variant-3-prime
rs1316779 -- 28,096,951(+) aggca(C/T)ggtag intron-variant
rs1319106 -- 28,062,217(-) CAGTC(A/G)GCAAC intron-variant
rs1319107 -- 28,062,175(-) GTTGC(A/G)TGCAG intron-variant
rs1320532 -- 28,068,662(-) TCTGA(A/G)CCAGG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for FLT3 Gene

Variant ID Type Subtype PubMed ID
esv275421 CNV Loss 21479260
esv1336289 CNV Insertion 17803354
nsv973 CNV Insertion 18451855
esv34052 CNV Loss 18971310
esv269085 CNV Insertion 20981092
esv2677792 CNV Deletion 23128226
nsv826599 CNV Loss 20364138
esv2674990 CNV Deletion 23128226

Relevant External Links for FLT3 Gene

HapMap Linkage Disequilibrium report
FLT3
Human Gene Mutation Database (HGMD)
FLT3

Disorders for FLT3 Gene

(2) OMIM Diseases for FLT3 Gene (136351)

UniProtKB/Swiss-Prot

FLT3_HUMAN
  • 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. {ECO:0000269 PubMed:11090077, ECO:0000269 PubMed:11290608, ECO:0000269 PubMed:11442493, ECO:0000269 PubMed:14504097, ECO:0000269 PubMed:16266983, ECO:0000269 PubMed:18305215, ECO:0000269 PubMed:8946930, ECO:0000269 PubMed:9737679}. 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.

(2) University of Copenhagen DISEASES for FLT3 Gene

(73) Novoseek inferred disease relationships for FLT3 Gene

Disease -log(P) Hits PubMed IDs
aml adult 85.2 20
leukemogenesis 81.6 24
aml childhood 80.8 25
leukemia 79.8 141
acute leukemia 73.4 46

Relevant External Links for FLT3

Genetic Association Database (GAD)
FLT3
Human Genome Epidemiology (HuGE) Navigator
FLT3
genes like me logo Genes that share disorders with FLT3: view

Publications for FLT3 Gene

  1. Human FLT3/FLK2 gene: cDNA cloning and expression in hematopoietic cells. (PMID: 8394751) Rosnet O. … Birnbaum D. (Blood 1993) 2 3 4 23
  2. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. (PMID: 8946930) Nakao M. … Misawa S. (Leukemia 1996) 3 4 23
  3. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. (PMID: 11290608) Yamamoto Y. … Naoe T. (Blood 2001) 3 4 23
  4. STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. (PMID: 7507245) Small D. … Civin C.I. (Proc. Natl. Acad. Sci. U.S.A. 1994) 3 4 23
  5. CYP1A1*2B (Val) allele is overrepresented in a subgroup of acute myeloid leukemia patients with poor-risk karyotype associated with NRAS mutation, but not associated with FLT3 internal tandem duplication. (PMID: 12468438) Bowen D.T. … Morgan G.J. (Blood 2003) 3 23 49

Products for FLT3 Gene

  • Addgene plasmids for FLT3

Sources for FLT3 Gene

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