UniProtKB - Q00342 (FLT3_MOUSE)
Protein
Receptor-type tyrosine-protein kinase FLT3
Gene
Flt3
Organism
Mus musculus (Mouse)
Status
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.5 Publications
Catalytic activityi
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]PROSITE-ProRule annotation1 PublicationEC:2.7.10.1PROSITE-ProRule annotation1 Publication
Activity regulationi
Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 645 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 814 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 617 – 625 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- cytokine receptor activity Source: UniProtKB
- glucocorticoid receptor binding Source: MGI
- phosphatidylinositol 3-kinase binding Source: MGI
- protein-containing complex binding Source: MGI
- protein self-association Source: MGI
- protein tyrosine kinase activity Source: MGI
- transmembrane receptor protein tyrosine kinase activity Source: GO_Central
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- antigen processing and presentation Source: MGI
- B cell differentiation Source: UniProtKB
- cellular response to cytokine stimulus Source: UniProtKB
- cellular response to virus Source: MGI
- common myeloid progenitor cell proliferation Source: UniProtKB
- cytokine-mediated signaling pathway Source: UniProtKB
- dendritic cell differentiation Source: UniProtKB
- dendritic cell homeostasis Source: MGI
- hematopoietic progenitor cell differentiation Source: GO_Central
- hemopoiesis Source: MGI
- homeostasis of number of cells within a tissue Source: MGI
- leukocyte differentiation Source: GO_Central
- leukocyte homeostasis Source: UniProtKB
- lymph node development Source: MGI
- lymphocyte differentiation Source: MGI
- lymphocyte proliferation Source: UniProtKB
- lymphoid progenitor cell differentiation Source: MGI
- myeloid progenitor cell differentiation Source: UniProtKB
- negative regulation of B cell differentiation Source: MGI
- negative regulation of cell population proliferation Source: MGI
- negative regulation of interleukin-6 production Source: MGI
- negative regulation of tumor necrosis factor production Source: MGI
- positive regulation of cell population proliferation Source: GO_Central
- positive regulation of ERK1 and ERK2 cascade Source: GO_Central
- positive regulation of interferon-alpha production Source: MGI
- positive regulation of interferon-alpha secretion Source: MGI
- positive regulation of interferon-gamma production Source: MGI
- positive regulation of interferon-gamma secretion Source: MGI
- positive regulation of interleukin-12 production Source: MGI
- positive regulation of interleukin-12 secretion Source: MGI
- positive regulation of MAPK cascade Source: GO_Central
- positive regulation of multicellular organism growth Source: MGI
- positive regulation of protein phosphorylation Source: MGI
- post-embryonic development Source: MGI
- pro-B cell differentiation Source: UniProtKB
- pro-T cell differentiation Source: MGI
- protein autophosphorylation Source: MGI
- spleen development Source: MGI
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Keywordsi
Molecular function | Kinase, Receptor, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.1 3474 |
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 Tyrosine-protein kinase receptor flk-2 CD_antigen: CD135 |
Gene namesi | Name:Flt3 Synonyms:Flk-2, Flt-3 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:95559 Flt3 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum lumen By similarity
Other locations
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 (By similarity).By similarity
Cytosol
- cytosol Source: MGI
Endoplasmic reticulum
- endoplasmic reticulum Source: MGI
- endoplasmic reticulum lumen Source: UniProtKB-SubCell
Nucleus
- nucleus Source: MGI
Plasma Membrane
- external side of plasma membrane Source: MGI
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: MGI
Other locations
- cell surface Source: MGI
- cytoplasm Source: MGI
- protein-containing complex Source: MGI
- receptor complex Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 28 – 544 | ExtracellularSequence analysisAdd BLAST | 517 | |
Transmembranei | 545 – 564 | HelicalSequence analysisAdd BLAST | 20 | |
Topological domaini | 565 – 992 | CytoplasmicSequence analysisAdd BLAST | 428 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Disruption phenotypei
No visible phenotype. Mice are born at the expected Mendelian rate, develop normally and are fertile. They show normal blood cell counts, excepting reduced levels of primitive B-cell progenitors. Mice lacking both Flt3 and Kit show a reduction in both lymphoid and myeloid cell lineages. They appear normal, but are born at a lower frequency than expected and exhibit severely reduced viability after 3 weeks, none surviving more than six weeks.1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 645 | K → A: Loss of kinase activity; no effect on FIZ1-binding. 1 Publication | 1 |
Keywords - Diseasei
Proto-oncogeneChemistry databases
ChEMBLi | CHEMBL2034796 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 27 | Sequence analysisAdd BLAST | 27 | |
ChainiPRO_0000016779 | 28 – 1000 | Receptor-type tyrosine-protein kinase FLT3Add BLAST | 973 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 36 ↔ 66 | PROSITE-ProRule annotation | ||
Glycosylationi | 44 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 104 ↔ 115 | PROSITE-ProRule annotation | ||
Glycosylationi | 133 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 152 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 200 ↔ 207 | PROSITE-ProRule annotation | ||
Disulfide bondi | 273 ↔ 331 | PROSITE-ProRule annotation | ||
Glycosylationi | 307 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 324 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 352 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 369 ↔ 408 | PROSITE-ProRule annotation | ||
Disulfide bondi | 382 ↔ 393 | PROSITE-ProRule annotation | ||
Glycosylationi | 445 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 474 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 503 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 542 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 573 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 575 | PhosphoserineBy similarity | 1 | |
Modified residuei | 590 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 592 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 600 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 727 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 760 | PhosphoserineBy similarity | 1 | |
Modified residuei | 769 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 796 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 845 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 958 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 972 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 1000 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
N-glycosylated, contains complex N-glycans with sialic acid.By similarity
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 (By similarity).By similarity
Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation.By similarity
Keywords - PTMi
Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | Q00342 |
PaxDbi | Q00342 |
PRIDEi | Q00342 |
PTM databases
iPTMneti | Q00342 |
PhosphoSitePlusi | Q00342 |
Expressioni
Tissue specificityi
Hematopoietic stem and progenitor cell-enriched populations. Found in brain, placenta and testis.
Interactioni
Subunit structurei
Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1 following ligand activation. Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2 (By similarity). Interacts with RNF115 and RNF126.By similarity1 Publication
GO - Molecular functioni
- glucocorticoid receptor binding Source: MGI
- phosphatidylinositol 3-kinase binding Source: MGI
- protein self-association Source: MGI
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 199707, 3 interactors |
STRINGi | 10090.ENSMUSP00000039041 |
Chemistry databases
BindingDBi | Q00342 |
Structurei
3D structure databases
ProteinModelPortali | Q00342 |
SMRi | Q00342 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 254 – 344 | Ig-like C2-typeAdd BLAST | 91 | |
Domaini | 611 – 946 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 336 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 592 – 598 | Important for normal regulation of the kinase activity and for maintaining the kinase in an inactive state in the absence of ligand bindingBy similarity | 7 |
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 (By similarity).By similarity
Sequence similaritiesi
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation
Keywords - Domaini
Immunoglobulin domain, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0200 Eukaryota COG0515 LUCA |
HOVERGENi | HBG005735 |
InParanoidi | Q00342 |
KOi | K05092 |
OrthoDBi | 236292at2759 |
Family and domain databases
Gene3Di | 2.60.40.10, 2 hits |
InterProi | View protein in InterPro IPR030118 FLT3 IPR007110 Ig-like_dom IPR036179 Ig-like_dom_sf IPR013783 Ig-like_fold IPR003599 Ig_sub IPR013151 Immunoglobulin IPR011009 Kinase-like_dom_sf 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 |
PANTHERi | PTHR24416:SF356 PTHR24416:SF356, 1 hit |
Pfami | View protein in Pfam PF00047 ig, 1 hit PF07714 Pkinase_Tyr, 1 hit |
SMARTi | View protein in SMART SM00409 IG, 2 hits SM00219 TyrKc, 1 hit |
SUPFAMi | SSF48726 SSF48726, 2 hits SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50835 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 |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q00342-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MRALAQRSDR RLLLLVVLSV MILETVTNQD LPVIKCVLIS HENNGSSAGK
60 70 80 90 100
PSSYRMVRGS PEDLQCTPRR QSEGTVYEAA TVEVAESGSI TLQVQLATPG
110 120 130 140 150
DLSCLWVFKH SSLGCQPHFD LQNRGIVSMA ILNVTETQAG EYLLHIQSEA
160 170 180 190 200
ANYTVLFTVN VRDTQLYVLR RPYFRKMENQ DALLCISEGV PEPTVEWVLC
210 220 230 240 250
SSHRESCKEE GPAVVRKEEK VLHELFGTDI RCCARNALGR ESTKLFTIDL
260 270 280 290 300
NQAPQSTLPQ LFLKVGEPLW IRCKAIHVNH GFGLTWELED KALEEGSYFE
310 320 330 340 350
MSTYSTNRTM IRILLAFVSS VGRNDTGYYT CSSSKHPSQS ALVTILEKGF
360 370 380 390 400
INATSSQEEY EIDPYEKFCF SVRFKAYPRI RCTWIFSQAS FPCEQRGLED
410 420 430 440 450
GYSISKFCDH KNKPGEYIFY AENDDAQFTK MFTLNIRKKP QVLANASASQ
460 470 480 490 500
ASCSSDGYPL PSWTWKKCSD KSPNCTEEIP EGVWNKKANR KVFGQWVSSS
510 520 530 540 550
TLNMSEAGKG LLVKCCAYNS MGTSCETIFL NSPGPFPFIQ DNISFYATIG
560 570 580 590 600
LCLPFIVVLI VLICHKYKKQ FRYESQLQMI QVTGPLDNEY FYVDFRDYEY
610 620 630 640 650
DLKWEFPREN LEFGKVLGSG AFGRVMNATA YGISKTGVSI QVAVKMLKEK
660 670 680 690 700
ADSCEKEALM SELKMMTHLG HHDNIVNLLG ACTLSGPVYL IFEYCCYGDL
710 720 730 740 750
LNYLRSKREK FHRTWTEIFK EHNFSFYPTF QAHSNSSMPG SREVQLHPPL
760 770 780 790 800
DQLSGFNGNS IHSEDEIEYE NQKRLAEEEE EDLNVLTFED LLCFAYQVAK
810 820 830 840 850
GMEFLEFKSC VHRDLAARNV LVTHGKVVKI CDFGLARDIL SDSSYVVRGN
860 870 880 890 900
ARLPVKWMAP ESLFEGIYTI KSDVWSYGIL LWEIFSLGVN PYPGIPVDAN
910 920 930 940 950
FYKLIQSGFK MEQPFYATEG IYFVMQSCWA FDSRKRPSFP NLTSFLGCQL
960 970 980 990 1000
AEAEEAMYQN MGGNVPEHPS IYQNRRPLSR EAGSEPPSPQ AQVKIHRERS
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketQ3UEW6 | Q3UEW6_MOUSE | Receptor-type tyrosine-protein kina... | Flt3 | 1,000 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 150 | A → R in AAA37634 (PubMed:1648448).Curated | 1 | |
Sequence conflicti | 242 | S → C in AAA37634 (PubMed:1648448).Curated | 1 | |
Sequence conflicti | 726 | F → S in AAA37634 (PubMed:1648448).Curated | 1 | |
Sequence conflicti | 957 – 991 | MYQNM…PSPQA → CIRTSIHLPKQAAPQQRGGL RAQSPQR in AAA37634 (PubMed:1648448).CuratedAdd BLAST | 35 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M64689 mRNA Translation: AAA37634.1 X59398 mRNA Translation: CAA42041.1 |
CCDSi | CCDS39400.1 |
PIRi | A39931 S18827 |
RefSeqi | NP_034359.2, NM_010229.2 |
UniGenei | Mm.194 |
Genome annotation databases
GeneIDi | 14255 |
KEGGi | mmu:14255 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M64689 mRNA Translation: AAA37634.1 X59398 mRNA Translation: CAA42041.1 |
CCDSi | CCDS39400.1 |
PIRi | A39931 S18827 |
RefSeqi | NP_034359.2, NM_010229.2 |
UniGenei | Mm.194 |
3D structure databases
ProteinModelPortali | Q00342 |
SMRi | Q00342 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 199707, 3 interactors |
STRINGi | 10090.ENSMUSP00000039041 |
Chemistry databases
BindingDBi | Q00342 |
ChEMBLi | CHEMBL2034796 |
PTM databases
iPTMneti | Q00342 |
PhosphoSitePlusi | Q00342 |
Proteomic databases
jPOSTi | Q00342 |
PaxDbi | Q00342 |
PRIDEi | Q00342 |
Protocols and materials databases
DNASUi | 14255 |
Structural Biology Knowledgebase | Search... |
Genome annotation databases
GeneIDi | 14255 |
KEGGi | mmu:14255 |
Organism-specific databases
CTDi | 2322 |
MGIi | MGI:95559 Flt3 |
Phylogenomic databases
eggNOGi | KOG0200 Eukaryota COG0515 LUCA |
HOVERGENi | HBG005735 |
InParanoidi | Q00342 |
KOi | K05092 |
OrthoDBi | 236292at2759 |
Enzyme and pathway databases
BRENDAi | 2.7.10.1 3474 |
Miscellaneous databases
PROi | PR:Q00342 |
SOURCEi | Search... |
Family and domain databases
Gene3Di | 2.60.40.10, 2 hits |
InterProi | View protein in InterPro IPR030118 FLT3 IPR007110 Ig-like_dom IPR036179 Ig-like_dom_sf IPR013783 Ig-like_fold IPR003599 Ig_sub IPR013151 Immunoglobulin IPR011009 Kinase-like_dom_sf 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 |
PANTHERi | PTHR24416:SF356 PTHR24416:SF356, 1 hit |
Pfami | View protein in Pfam PF00047 ig, 1 hit PF07714 Pkinase_Tyr, 1 hit |
SMARTi | View protein in SMART SM00409 IG, 2 hits SM00219 TyrKc, 1 hit |
SUPFAMi | SSF48726 SSF48726, 2 hits SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50835 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 |
ProtoNeti | Search... |
Entry informationi
Entry namei | FLT3_MOUSE | |
Accessioni | Q00342Primary (citable) accession number: Q00342 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1993 |
Last sequence update: | April 1, 2015 | |
Last modified: | February 13, 2019 | |
This is version 165 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - SIMILARITY comments
Index of protein domains and families - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot