Receptor-type tyrosine-protein kinase FLT3

Details

Name
Receptor-type tyrosine-protein kinase FLT3
Kind
protein
Synonyms
  • 2.7.10.1
  • CD135
  • Fetal liver kinase-2
  • FL cytokine receptor
  • FLK-2
  • FLK2
  • FLT-3
  • Fms-like tyrosine kinase 3
  • Stem cell tyrosine kinase 1
  • STK-1
  • STK1
Gene Name
FLT3
UniProtKB Entry
P36888Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0036960|Receptor-type tyrosine-protein kinase FLT3
MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKSSSYPMVSESP
EDLGCALRPQSSGTVYEAAAVEVDVSASITLQVLVDAPGNISCLWVFKHSSLNCQPHFDL
QNRGVVSMVILKMTETQAGEYLLFIQSEATNYTILFTVSIRNTLLYTLRRPYFRKMENQD
ALVCISESVPEPIVEWVLCDSQGESCKEESPAVVKKEEKVLHELFGTDIRCCARNELGRE
CTRLFTIDLNQTPQTTLPQLFLKVGEPLWIRCKAVHVNHGFGLTWELENKALEEGNYFEM
STYSTNRTMIRILFAFVSSVARNDTGYYTCSSSKHPSQSALVTIVEKGFINATNSSEDYE
IDQYEEFCFSVRFKAYPQIRCTWTFSRKSFPCEQKGLDNGYSISKFCNHKHQPGEYIFHA
ENDDAQFTKMFTLNIRRKPQVLAEASASQASCFSDGYPLPSWTWKKCSDKSPNCTEEITE
GVWNRKANRKVFGQWVSSSTLNMSEAIKGFLVKCCAYNSLGTSCETILLNSPGPFPFIQD
NISFYATIGVCLLFIVVLTLLICHKYKKQFRYESQLQMVQVTGSSDNEYFYVDFREYEYD
LKWEFPRENLEFGKVLGSGAFGKVMNATAYGISKTGVSIQVAVKMLKEKADSSEREALMS
ELKMMTQLGSHENIVNLLGACTLSGPIYLIFEYCCYGDLLNYLRSKREKFHRTWTEIFKE
HNFSFYPTFQSHPNSSMPGSREVQIHPDSDQISGLHGNSFHSEDEIEYENQKRLEEEEDL
NVLTFEDLLCFAYQVAKGMEFLEFKSCVHRDLAARNVLVTHGKVVKICDFGLARDIMSDS
NYVVRGNARLPVKWMAPESLFEGIYTIKSDVWSYGILLWEIFSLGVNPYPGIPVDANFYK
LIQNGFKMDQPFYATEEIYIIMQSCWAFDSRKRPSFPNLTSFLGCQLADAEEAMYQNVDG
RVSECPHTYQNRRPFSREMDLGLLSPQAQVEDS
Number of residues
993
Molecular Weight
112902.51
Theoretical pI
5.5
GO Classification
Functions
ATP binding / cytokine receptor activity / transmembrane receptor protein tyrosine kinase activity
Processes
B cell differentiation / cellular response to cytokine stimulus / common myeloid progenitor cell proliferation / cytokine-mediated signaling pathway / dendritic cell differentiation / hemopoiesis / leukocyte homeostasis / lymphocyte proliferation / myeloid progenitor cell differentiation / peptidyl-tyrosine phosphorylation / positive regulation of MAP kinase activity / positive regulation of MAPK cascade / positive regulation of tyrosine phosphorylation of STAT protein / pro-B cell differentiation / protein autophosphorylation / regulation of apoptotic process
Components
endoplasmic reticulum lumen
General Function
Tyrosine-protein kinase that acts as a 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
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
1-26
Transmembrane Regions
544-563
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0018920|Receptor-type tyrosine-protein kinase FLT3 (FLT3)
ATGCCGGCGTTGGCGCGCGACGGCGGCCAGCTGCCGCTGCTCGTTGTTTTTTCTGCAATG
ATATTTGGGACTATTACAAATCAAGATCTGCCTGTGATCAAGTGTGTTTTAATCAATCAT
AAGAACAATGATTCATCAGTGGGGAAGTCATCATCATATCCCATGGTATCAGAATCCCCG
GAAGACCTCGGGTGTGCGTTGAGACCCCAGAGCTCAGGGACAGTGTACGAAGCTGCCGCT
GTGGAAGTGGATGTATCTGCTTCCATCACACTGCAAGTGCTGGTCGACGCCCCAGGGAAC
ATTTCCTGTCTCTGGGTCTTTAAGCACAGCTCCCTGAATTGCCAGCCACATTTTGATTTA
CAAAACAGAGGAGTTGTTTCCATGGTCATTTTGAAAATGACAGAAACCCAAGCTGGAGAA
TACCTACTTTTTATTCAGAGTGAAGCTACCAATTACACAATATTGTTTACAGTGAGTATA
AGAAATACCCTGCTTTACACATTAAGAAGACCTTACTTTAGAAAAATGGAAAACCAGGAC
GCCCTGGTCTGCATATCTGAGAGCGTTCCAGAGCCGATCGTGGAATGGGTGCTTTGCGAT
TCACAGGGGGAAAGCTGTAAAGAAGAAAGTCCAGCTGTTGTTAAAAAGGAGGAAAAAGTG
CTTCATGAATTATTTGGGACGGACATAAGGTGCTGTGCCAGAAATGAACTGGGCAGGGAA
TGCACCAGGCTGTTCACAATAGATCTAAATCAAACTCCTCAGACCACATTGCCACAATTA
TTTCTTAAAGTAGGGGAACCCTTATGGATAAGGTGCAAAGCTGTTCATGTGAACCATGGA
TTCGGGCTCACCTGGGAATTAGAAAACAAAGCACTCGAGGAGGGCAACTACTTTGAGATG
AGTACCTATTCAACAAACAGAACTATGATACGGATTCTGTTTGCTTTTGTATCATCAGTG
GCAAGAAACGACACCGGATACTACACTTGTTCCTCTTCAAAGCATCCCAGTCAATCAGCT
TTGGTTACCATCGTAGAAAAGGGATTTATAAATGCTACCAATTCAAGTGAAGATTATGAA
ATTGACCAATATGAAGAGTTTTGTTTTTCTGTCAGGTTTAAAGCCTACCCACAAATCAGA
TGTACGTGGACCTTCTCTCGAAAATCATTTCCTTGTGAGCAAAAGGGTCTTGATAACGGA
TACAGCATATCCAAGTTTTGCAATCATAAGCACCAGCCAGGAGAATATATATTCCATGCA
GAAAATGATGATGCCCAATTTACCAAAATGTTCACGCTGAATATAAGAAGGAAACCTCAA
GTGCTCGCAGAAGCATCGGCAAGTCAGGCGTCCTGTTTCTCGGATGGATACCCATTACCA
TCTTGGACCTGGAAGAAGTGTTCAGACAAGTCTCCCAACTGCACAGAAGAGATCACAGAA
GGAGTCTGGAATAGAAAGGCTAACAGAAAAGTGTTTGGACAGTGGGTGTCGAGCAGTACT
CTAAACATGAGTGAAGCCATAAAAGGGTTCCTGGTCAAGTGCTGTGCATACAATTCCCTT
GGCACATCTTGTGAGACGATCCTTTTAAACTCTCCAGGCCCCTTCCCTTTCATCCAAGAC
AACATCTCATTCTATGCAACAATTGGTGTTTGTCTCCTCTTCATTGTCGTTTTAACCCTG
CTAATTTGTCACAAGTACAAAAAGCAATTTAGGTATGAAAGCCAGCTACAGATGGTACAG
GTGACCGGCTCCTCAGATAATGAGTACTTCTACGTTGATTTCAGAGAATATGAATATGAT
CTCAAATGGGAGTTTCCAAGAGAAAATTTAGAGTTTGGGAAGGTACTAGGATCAGGTGCT
TTTGGAAAAGTGATGAACGCAACAGCTTATGGAATTAGCAAAACAGGAGTCTCAATCCAG
GTTGCCGTCAAAATGCTGAAAGAAAAAGCAGACAGCTCTGAAAGAGAGGCACTCATGTCA
GAACTCAAGATGATGACCCAGCTGGGAAGCCACGAGAATATTGTGAACCTGCTGGGGGCG
TGCACACTGTCAGGACCAATTTACTTGATTTTTGAATACTGTTGCTATGGTGATCTTCTC
AACTATCTAAGAAGTAAAAGAGAAAAATTTCACAGGACTTGGACAGAGATTTTCAAGGAA
CACAATTTCAGTTTTTACCCCACTTTCCAATCACATCCAAATTCCAGCATGCCTGGTTCA
AGAGAAGTTCAGATACACCCGGACTCGGATCAAATCTCAGGGCTTCATGGGAATTCATTT
CACTCTGAAGATGAAATTGAATATGAAAACCAAAAAAGGCTGGAAGAAGAGGAGGACTTG
AATGTGCTTACATTTGAAGATCTTCTTTGCTTTGCATATCAAGTTGCCAAAGGAATGGAA
TTTCTGGAATTTAAGTCGTGTGTTCACAGAGACCTGGCCGCCAGGAACGTGCTTGTCACC
CACGGGAAAGTGGTGAAGATATGTGACTTTGGATTGGCTCGAGATATCATGAGTGATTCC
AACTATGTTGTCAGGGGCAATGCCCGTCTGCCTGTAAAATGGATGGCCCCCGAAAGCCTG
TTTGAAGGCATCTACACCATTAAGAGTGATGTCTGGTCATATGGAATATTACTGTGGGAA
ATCTTCTCACTTGGTGTGAATCCTTACCCTGGCATTCCGGTTGATGCTAACTTCTACAAA
CTGATTCAAAATGGATTTAAAATGGATCAGCCATTTTATGCTACAGAAGAAATATACATT
ATAATGCAATCCTGCTGGGCTTTTGACTCAAGGAAACGGCCATCCTTCCCTAATTTGACT
TCGTTTTTAGGATGTCAGCTGGCAGATGCAGAAGAAGCGATGTATCAGAATGTGGATGGC
CGTGTTTCGGAATGTCCTCACACCTACCAAAACAGGCGACCTTTCAGCAGAGAGATGGAT
TTGGGGCTACTCTCTCCGCAGGCTCAGGTCGAAGATTCGTAG
Chromosome Location
13
Locus
13q12.2
External Identifiers
ResourceLink
UniProtKB IDP36888
UniProtKB Entry NameFLT3_HUMAN
GenBank Protein ID409573
GenBank Gene IDU02687
GeneCard IDFLT3
GenAtlas IDFLT3
HGNC IDHGNC:3765
PDB ID(s)1RJB, 3QS7, 3QS9, 4RT7, 4XUF, 5X02, 6IL3, 6JQR, 7QDP, 7ZV9
KEGG IDhsa:2322
IUPHAR/Guide To Pharmacology ID1807
NCBI Gene ID2322
General References
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  8. Kiyoi H, Towatari M, Yokota S, Hamaguchi M, Ohno R, Saito H, Naoe T: Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia. 1998 Sep;12(9):1333-7. [Article]
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  14. Heiss E, Masson K, Sundberg C, Pedersen M, Sun J, Bengtsson S, Ronnstrand L: Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2. Blood. 2006 Sep 1;108(5):1542-50. Epub 2006 May 9. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
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4SC-203investigationalyestargetmodulatorDetails
FN-1501investigationalyestargetinhibitorDetails
FF-10101-01investigationalyestargetinhibitorDetails
BMS-690514investigationalyestargetinhibitorDetails
FamitinibinvestigationalyestargetinhibitorDetails
MivavotinibinvestigationalyestargetinhibitorDetails
ZidovudineapprovedyestargetbinderDetails