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Protein

Receptor-type tyrosine-protein kinase FLT3

Gene

FLT3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.11 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

Enzyme regulationi

Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei644ATPCurated1
Active sitei811Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi616 – 624ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cytokine receptor activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
  • vascular endothelial growth factor-activated receptor activity Source: ProtInc

GO - Biological processi

  • animal organ regeneration Source: Ensembl
  • B cell differentiation Source: UniProtKB
  • cellular response to cytokine stimulus Source: UniProtKB
  • cellular response to glucocorticoid stimulus Source: Ensembl
  • common myeloid progenitor cell proliferation Source: UniProtKB
  • cytokine-mediated signaling pathway Source: UniProtKB
  • dendritic cell differentiation Source: UniProtKB
  • hemopoiesis Source: MGI
  • leukocyte homeostasis Source: UniProtKB
  • lymphocyte proliferation Source: UniProtKB
  • myeloid progenitor cell differentiation Source: UniProtKB
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of MAP kinase activity Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of tyrosine phosphorylation of STAT protein Source: UniProtKB
  • pro-B cell differentiation Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of apoptotic process Source: UniProtKB
  • response to organonitrogen compound Source: Ensembl
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS04540-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-449147. Signaling by Interleukins.
SignaLinkiP36888.
SIGNORiP36888.

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein kinase FLT3 (EC:2.7.10.1)
Alternative name(s):
FL cytokine receptor
Fetal liver kinase-2
Short name:
FLK-2
Fms-like tyrosine kinase 3
Short name:
FLT-3
Stem cell tyrosine kinase 1
Short name:
STK-1
CD_antigen: CD135
Gene namesi
Name:FLT3
Synonyms:CD135, FLK2, STK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:3765. FLT3.

Subcellular locationi

  • 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.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini27 – 543ExtracellularSequence analysisAdd BLAST517
Transmembranei544 – 563HelicalSequence analysisAdd BLAST20
Topological domaini564 – 993CytoplasmicSequence analysisAdd BLAST430

GO - Cellular componenti

  • cytosol Source: Ensembl
  • endoplasmic reticulum lumen Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: ProtInc
  • nucleus Source: Ensembl
  • plasma membrane Source: Reactome
  • protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Leukemia, acute myelogenous (AML)8 Publications
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.
Disease descriptionA 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.
See also OMIM:601626

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi589Y → F: Reduced phosphorylation of the wild-type kinase in response to ligand binding. No effect on the phosphorylation of the constitutively activated mutant kinase variants. Abolishes activation of STAT5A. 3 Publications1
Mutagenesisi591Y → F: No significant effect on tyrosine phosphorylation. Abolishes activation of STAT5A. 2 Publications1
Mutagenesisi599Y → F: Abolishes interaction with PTPN11/SHP2 and phosphorylation of PTPN11/SHP2. 1 Publication1
Mutagenesisi644K → A: Abolishes kinase activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi2322.
MalaCardsiFLT3.
MIMi601626. phenotype.
OpenTargetsiENSG00000122025.
Orphaneti98829. 'Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)'.
102724. 'Acute myeloid leukemia with t(8;21)(q22;q22) translocation'.
98837. Acute biphenotypic leukemia.
98834. Acute myeloblastic leukemia with maturation.
98833. Acute myeloblastic leukemia without maturation.
98832. Minimally differentiated acute myeloblastic leukemia.
99860. Precursor B-cell acute lymphoblastic leukemia.
99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA28181.

Chemistry databases

ChEMBLiCHEMBL1974.
DrugBankiDB09079. Nintedanib.
DB08901. Ponatinib.
DB00398. Sorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi1807.

Polymorphism and mutation databases

BioMutaiFLT3.
DMDMi156630887.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000001677827 – 993Receptor-type tyrosine-protein kinase FLT3Add BLAST967

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 65PROSITE-ProRule annotation1 Publication
Glycosylationi43N-linked (GlcNAc...)1 Publication1
Glycosylationi100N-linked (GlcNAc...)1 Publication1
Disulfide bondi103 ↔ 114PROSITE-ProRule annotation1 Publication
Glycosylationi151N-linked (GlcNAc...)1 Publication1
Disulfide bondi199 ↔ 206PROSITE-ProRule annotation1 Publication
Disulfide bondi232 ↔ 241PROSITE-ProRule annotation1 Publication
Disulfide bondi272 ↔ 330PROSITE-ProRule annotation1 Publication
Glycosylationi306N-linked (GlcNAc...)1 Publication1
Glycosylationi323N-linked (GlcNAc...)1 Publication1
Glycosylationi351N-linked (GlcNAc...)1 Publication1
Glycosylationi354N-linked (GlcNAc...)1 Publication1
Disulfide bondi368 ↔ 407PROSITE-ProRule annotation1 Publication
Disulfide bondi381 ↔ 392PROSITE-ProRule annotation1 Publication
Glycosylationi473N-linked (GlcNAc...)1
Glycosylationi502N-linked (GlcNAc...)1
Glycosylationi541N-linked (GlcNAc...)Sequence analysis1
Modified residuei572Phosphotyrosine2 Publications1
Modified residuei574Phosphoserine1 Publication1
Modified residuei589Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei591Phosphotyrosine; by autocatalysis5 Publications1
Modified residuei599Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei726Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei759PhosphoserineCombined sources1
Modified residuei768Phosphotyrosine2 Publications1
Modified residuei793Phosphotyrosine2 Publications1
Modified residuei842Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei955Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei969Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei993PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated, contains complex N-glycans with sialic acid.3 Publications
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.
Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP36888.
PaxDbiP36888.
PeptideAtlasiP36888.
PRIDEiP36888.

PTM databases

iPTMnetiP36888.
PhosphoSitePlusiP36888.

Expressioni

Tissue specificityi

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.4 Publications

Gene expression databases

BgeeiENSG00000122025.
CleanExiHS_FLT3.
ExpressionAtlasiP36888. baseline and differential.
GenevisibleiP36888. HS.

Organism-specific databases

HPAiCAB018358.

Interactioni

Subunit structurei

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).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
IKBKGQ9Y6K92EBI-3946257,EBI-81279
PIK3R1P279862EBI-3946257,EBI-79464
PTPRJQ129133EBI-3946257,EBI-2264500
SYKP4340521EBI-3946257,EBI-78302

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi108610. 11 interactors.
DIPiDIP-59769N.
IntActiP36888. 5 interactors.
MINTiMINT-7103562.
STRINGi9606.ENSP00000241453.

Chemistry databases

BindingDBiP36888.

Structurei

Secondary structure

1993
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi575 – 581Combined sources7
Beta strandi583 – 585Combined sources3
Beta strandi589 – 591Combined sources3
Helixi594 – 596Combined sources3
Helixi601 – 603Combined sources3
Helixi607 – 609Combined sources3
Beta strandi610 – 618Combined sources9
Beta strandi620 – 631Combined sources12
Beta strandi633 – 636Combined sources4
Beta strandi638 – 646Combined sources9
Helixi656 – 668Combined sources13
Beta strandi677 – 681Combined sources5
Beta strandi683 – 686Combined sources4
Beta strandi688 – 692Combined sources5
Helixi699 – 704Combined sources6
Turni705 – 708Combined sources4
Helixi785 – 804Combined sources20
Beta strandi807 – 809Combined sources3
Helixi814 – 816Combined sources3
Beta strandi817 – 820Combined sources4
Turni821 – 823Combined sources3
Beta strandi824 – 827Combined sources4
Helixi831 – 833Combined sources3
Helixi836 – 838Combined sources3
Beta strandi842 – 845Combined sources4
Beta strandi848 – 850Combined sources3
Helixi852 – 854Combined sources3
Helixi857 – 862Combined sources6
Helixi867 – 881Combined sources15
Turni882 – 884Combined sources3
Helixi896 – 903Combined sources8
Helixi916 – 924Combined sources9
Helixi930 – 932Combined sources3
Helixi936 – 949Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RJBX-ray2.10A564-907[»]
3QS7X-ray4.30E/F/G/H27-436[»]
3QS9X-ray7.80E/F/G/H27-540[»]
4RT7X-ray3.10A564-958[»]
4XUFX-ray3.20A/B600-947[»]
DisProtiDP00312.
ProteinModelPortaliP36888.
SMRiP36888.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP36888.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini253 – 343Ig-like C2-typeAdd BLAST91
Domaini610 – 943Protein kinasePROSITE-ProRule annotationAdd BLAST334

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni591 – 597Important for normal regulation of the kinase activity and for maintaining the kinase in an inactive state in the absence of bound ligand7

Domaini

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.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOVERGENiHBG005735.
InParanoidiP36888.
KOiK05092.
OMAiGPIYLIF.
OrthoDBiEOG091G01TL.
PhylomeDBiP36888.
TreeFamiTF325768.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR030118. FLT3.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PANTHERiPTHR24416:SF356. PTHR24416:SF356. 2 hits.
PfamiPF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P36888-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPALARDGGQ LPLLVVFSAM IFGTITNQDL PVIKCVLINH KNNDSSVGKS
60 70 80 90 100
SSYPMVSESP EDLGCALRPQ SSGTVYEAAA VEVDVSASIT LQVLVDAPGN
110 120 130 140 150
ISCLWVFKHS SLNCQPHFDL QNRGVVSMVI LKMTETQAGE YLLFIQSEAT
160 170 180 190 200
NYTILFTVSI RNTLLYTLRR PYFRKMENQD ALVCISESVP EPIVEWVLCD
210 220 230 240 250
SQGESCKEES PAVVKKEEKV LHELFGTDIR CCARNELGRE CTRLFTIDLN
260 270 280 290 300
QTPQTTLPQL FLKVGEPLWI RCKAVHVNHG FGLTWELENK ALEEGNYFEM
310 320 330 340 350
STYSTNRTMI RILFAFVSSV ARNDTGYYTC SSSKHPSQSA LVTIVEKGFI
360 370 380 390 400
NATNSSEDYE IDQYEEFCFS VRFKAYPQIR CTWTFSRKSF PCEQKGLDNG
410 420 430 440 450
YSISKFCNHK HQPGEYIFHA ENDDAQFTKM FTLNIRRKPQ VLAEASASQA
460 470 480 490 500
SCFSDGYPLP SWTWKKCSDK SPNCTEEITE GVWNRKANRK VFGQWVSSST
510 520 530 540 550
LNMSEAIKGF LVKCCAYNSL GTSCETILLN SPGPFPFIQD NISFYATIGV
560 570 580 590 600
CLLFIVVLTL LICHKYKKQF RYESQLQMVQ VTGSSDNEYF YVDFREYEYD
610 620 630 640 650
LKWEFPRENL EFGKVLGSGA FGKVMNATAY GISKTGVSIQ VAVKMLKEKA
660 670 680 690 700
DSSEREALMS ELKMMTQLGS HENIVNLLGA CTLSGPIYLI FEYCCYGDLL
710 720 730 740 750
NYLRSKREKF HRTWTEIFKE HNFSFYPTFQ SHPNSSMPGS REVQIHPDSD
760 770 780 790 800
QISGLHGNSF HSEDEIEYEN QKRLEEEEDL NVLTFEDLLC FAYQVAKGME
810 820 830 840 850
FLEFKSCVHR DLAARNVLVT HGKVVKICDF GLARDIMSDS NYVVRGNARL
860 870 880 890 900
PVKWMAPESL FEGIYTIKSD VWSYGILLWE IFSLGVNPYP GIPVDANFYK
910 920 930 940 950
LIQNGFKMDQ PFYATEEIYI IMQSCWAFDS RKRPSFPNLT SFLGCQLADA
960 970 980 990
EEAMYQNVDG RVSECPHTYQ NRRPFSREMD LGLLSPQAQV EDS
Length:993
Mass (Da):112,903
Last modified:August 21, 2007 - v2
Checksum:i6C1995718F352ECE
GO
Isoform 2 (identifier: P36888-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     807-847: Missing.

Show »
Length:952
Mass (Da):108,378
Checksum:i1C384B292EDEB144
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8G → A in AAA18947 (PubMed:7507245).Curated1
Sequence conflicti10 – 11QL → TV in AAA18947 (PubMed:7507245).Curated2
Sequence conflicti71S → N in AAI44040 (PubMed:15489334).Curated1
Sequence conflicti78A → R in CAA81393 (PubMed:8394751).Curated1
Sequence conflicti346E → G in AAA18947 (PubMed:7507245).Curated1
Sequence conflicti940T → H in AAA35487 (PubMed:2004790).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0346777D → G.Corresponds to variant rs12872889dbSNPEnsembl.1
Natural variantiVAR_042069158V → A.1 PublicationCorresponds to variant rs56321896dbSNPEnsembl.1
Natural variantiVAR_054149194V → M.1 PublicationCorresponds to variant rs146030737dbSNPEnsembl.1
Natural variantiVAR_034678227T → M.4 PublicationsCorresponds to variant rs1933437dbSNPEnsembl.1
Natural variantiVAR_042070324D → N.1 PublicationCorresponds to variant rs35602083dbSNPEnsembl.1
Natural variantiVAR_042071358D → V.1 PublicationCorresponds to variant rs34172843dbSNPEnsembl.1
Natural variantiVAR_061291417I → L.Corresponds to variant rs56090538dbSNPEnsembl.1
Natural variantiVAR_042072557V → I.1 PublicationCorresponds to variant rs35958982dbSNPEnsembl.1
Natural variantiVAR_065679835D → E in acute lymphoblastic leukemia patients and in acute myelogenous leukemia patients; somatic mutation; constitutively activated. 2 PublicationsCorresponds to variant rs121913487dbSNPEnsembl.1
Natural variantiVAR_065680835D → H in acute lymphoblastic leukemia patients and in acute myelogenous leukemia patients; somatic mutation; constitutively activated. 3 PublicationsCorresponds to variant rs121913488dbSNPEnsembl.1
Natural variantiVAR_065681835D → N in acute lymphoblastic leukemia patients and in acute myelogenous leukemia patients; somatic mutation; constitutively activated. 1 PublicationCorresponds to variant rs121913488dbSNPEnsembl.1
Natural variantiVAR_065682835D → V in acute lymphoblastic leukemia patients and in acute myelogenous leukemia patients; somatic mutation; constitutively activated. 1 PublicationCorresponds to variant rs121909646dbSNPEnsembl.1
Natural variantiVAR_065683835D → Y in acute lymphoblastic leukemia patients and in acute myelogenous leukemia patients; somatic mutation; constitutively activated. 3 PublicationsCorresponds to variant rs121913488dbSNPEnsembl.1
Natural variantiVAR_065684836I → M in acute lymphoblastic leukemia patients; somatic mutation. 1 PublicationCorresponds to variant rs121913232dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041796807 – 847Missing in isoform 2. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02687 mRNA. Translation: AAA18947.1.
Z26652 mRNA. Translation: CAA81393.1.
AL356915 Genomic DNA. No translation available.
AL445262 Genomic DNA. No translation available.
AL591024 Genomic DNA. No translation available.
CH471075 Genomic DNA. Translation: EAX08424.1.
BC126350 mRNA. Translation: AAI26351.1.
BC144039 mRNA. Translation: AAI44040.1.
BC144040 mRNA. Translation: AAI44041.1.
L36162 mRNA. Translation: AAA35487.1.
CCDSiCCDS31953.1. [P36888-1]
PIRiA36873.
A39061.
RefSeqiNP_004110.2. NM_004119.2. [P36888-1]
UniGeneiHs.507590.

Genome annotation databases

EnsembliENST00000241453; ENSP00000241453; ENSG00000122025. [P36888-1]
GeneIDi2322.
KEGGihsa:2322.
UCSCiuc001urw.3. human. [P36888-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02687 mRNA. Translation: AAA18947.1.
Z26652 mRNA. Translation: CAA81393.1.
AL356915 Genomic DNA. No translation available.
AL445262 Genomic DNA. No translation available.
AL591024 Genomic DNA. No translation available.
CH471075 Genomic DNA. Translation: EAX08424.1.
BC126350 mRNA. Translation: AAI26351.1.
BC144039 mRNA. Translation: AAI44040.1.
BC144040 mRNA. Translation: AAI44041.1.
L36162 mRNA. Translation: AAA35487.1.
CCDSiCCDS31953.1. [P36888-1]
PIRiA36873.
A39061.
RefSeqiNP_004110.2. NM_004119.2. [P36888-1]
UniGeneiHs.507590.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RJBX-ray2.10A564-907[»]
3QS7X-ray4.30E/F/G/H27-436[»]
3QS9X-ray7.80E/F/G/H27-540[»]
4RT7X-ray3.10A564-958[»]
4XUFX-ray3.20A/B600-947[»]
DisProtiDP00312.
ProteinModelPortaliP36888.
SMRiP36888.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108610. 11 interactors.
DIPiDIP-59769N.
IntActiP36888. 5 interactors.
MINTiMINT-7103562.
STRINGi9606.ENSP00000241453.

Chemistry databases

BindingDBiP36888.
ChEMBLiCHEMBL1974.
DrugBankiDB09079. Nintedanib.
DB08901. Ponatinib.
DB00398. Sorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi1807.

PTM databases

iPTMnetiP36888.
PhosphoSitePlusiP36888.

Polymorphism and mutation databases

BioMutaiFLT3.
DMDMi156630887.

Proteomic databases

MaxQBiP36888.
PaxDbiP36888.
PeptideAtlasiP36888.
PRIDEiP36888.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000241453; ENSP00000241453; ENSG00000122025. [P36888-1]
GeneIDi2322.
KEGGihsa:2322.
UCSCiuc001urw.3. human. [P36888-1]

Organism-specific databases

CTDi2322.
DisGeNETi2322.
GeneCardsiFLT3.
H-InvDBHIX0037338.
HGNCiHGNC:3765. FLT3.
HPAiCAB018358.
MalaCardsiFLT3.
MIMi136351. gene.
601626. phenotype.
neXtProtiNX_P36888.
OpenTargetsiENSG00000122025.
Orphaneti98829. 'Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)'.
102724. 'Acute myeloid leukemia with t(8;21)(q22;q22) translocation'.
98837. Acute biphenotypic leukemia.
98834. Acute myeloblastic leukemia with maturation.
98833. Acute myeloblastic leukemia without maturation.
98832. Minimally differentiated acute myeloblastic leukemia.
99860. Precursor B-cell acute lymphoblastic leukemia.
99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA28181.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOVERGENiHBG005735.
InParanoidiP36888.
KOiK05092.
OMAiGPIYLIF.
OrthoDBiEOG091G01TL.
PhylomeDBiP36888.
TreeFamiTF325768.

Enzyme and pathway databases

BioCyciZFISH:HS04540-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-449147. Signaling by Interleukins.
SignaLinkiP36888.
SIGNORiP36888.

Miscellaneous databases

EvolutionaryTraceiP36888.
GeneWikiiCD135.
GenomeRNAii2322.
PROiP36888.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000122025.
CleanExiHS_FLT3.
ExpressionAtlasiP36888. baseline and differential.
GenevisibleiP36888. HS.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR030118. FLT3.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PANTHERiPTHR24416:SF356. PTHR24416:SF356. 2 hits.
PfamiPF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFLT3_HUMAN
AccessioniPrimary (citable) accession number: P36888
Secondary accession number(s): A0AVG9
, B7ZLT7, B7ZLT8, F5H0A0, Q13414
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: August 21, 2007
Last modified: November 2, 2016
This is version 170 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Can be used as diagnostic tool to establish the exact cause of acute myeloid leukemia, and to determine the optimal therapy.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  8. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.