UniProt:P36888 FLT3

chain
  • signal peptide:1-26
  • chain:27-993
checksum 6C1995718F352ECE
comment
  • 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.ACTIVITY REGULATION Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation.SUBUNIT 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).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus protein UL7.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.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.PTM N-glycosylated, contains complex N-glycans with sialic acid.PTM 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.PTM Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation.MISCELLANEOUS Can be used as diagnostic tool to establish the exact cause of acute myeloid leukemia, and to determine the optimal therapy.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
crossReference
databaseName UniProt
dbId 54914
description
  • recommendedName: Receptor-type tyrosine-protein kinase FLT3 ecNumber2.7.10.1/ecNumber alternativeName: FL cytokine receptor alternativeName: Fetal liver kinase-2 shortName:FLK-2 alternativeName: Fms-like tyrosine kinase 3 shortName:FLT-3 alternativeName: Stem cell tyrosine kinase 1 shortName:STK-1 cdAntigenNameCD135/cdAntigenName
displayName UniProt:P36888 FLT3
geneName
  • FLT3
  • CD135
  • FLK2
  • STK1
identifier P36888
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • ATP-binding
  • Disease variant
  • Disulfide bond
  • Endoplasmic reticulum
  • Glycoprotein
  • Host-virus interaction
  • Immunoglobulin domain
  • Kinase
  • Membrane
  • Nucleotide-binding
  • Phosphoprotein
  • Proto-oncogene
  • Receptor
  • Reference proteome
  • Signal
  • Transferase
  • Transmembrane
  • Transmembrane helix
  • Tyrosine-protein kinase
  • Ubl conjugation
modified [InstanceEdit:11703684] Shorser, Solomon, 2021-05-28
name
  • FLT3
otherIdentifier
  • 0006290286
  • 1065_at
  • 11737027_a_at
  • 16777685
  • 206674_at
  • 2322
  • 34583_at
  • 3507201
  • 3507202
  • 3507205
  • 3507206
  • 3507207
  • 3507210
  • 3507211
  • 3507212
  • 3507213
  • 3507216
  • 3507217
  • 3507218
  • 3507219
  • 3507221
  • 3507222
  • 3507223
  • 3507224
  • 3507225
  • 3507226
  • 3507228
  • 3507229
  • 3507230
  • 3507231
  • 3507233
  • 3507234
  • 3507237
  • 3507239
  • 3507242
  • 3507243
  • 3507244
  • 7970737
  • GE58857
  • GO:0000165
  • GO:0000166
  • GO:0001776
  • GO:0002318
  • GO:0002328
  • GO:0002376
  • GO:0003674
  • GO:0004672
  • GO:0004713
  • GO:0004714
  • GO:0004896
  • GO:0005021
  • GO:0005515
  • GO:0005524
  • GO:0005575
  • GO:0005622
  • GO:0005634
  • GO:0005737
  • GO:0005768
  • GO:0005783
  • GO:0005788
  • GO:0005829
  • GO:0005886
  • GO:0005887
  • GO:0006464
  • GO:0006468
  • GO:0006629
  • GO:0007165
  • GO:0007169
  • GO:0007275
  • GO:0008134
  • GO:0008150
  • GO:0008219
  • GO:0008283
  • GO:0008284
  • GO:0010008
  • GO:0010243
  • GO:0014068
  • GO:0016020
  • GO:0016021
  • GO:0016032
  • GO:0016301
  • GO:0016310
  • GO:0016740
  • GO:0018108
  • GO:0019221
  • GO:0019838
  • GO:0030097
  • GO:0030154
  • GO:0030183
  • GO:0031100
  • GO:0031410
  • GO:0032991
  • GO:0033674
  • GO:0035259
  • GO:0035726
  • GO:0038084
  • GO:0042531
  • GO:0042592
  • GO:0042981
  • GO:0043167
  • GO:0043226
  • GO:0043235
  • GO:0043406
  • GO:0043410
  • GO:0043552
  • GO:0043621
  • GO:0044403
  • GO:0044877
  • GO:0046651
  • GO:0046777
  • GO:0048856
  • GO:0051897
  • GO:0071345
  • GO:0071385
  • GO:0097028
  • HMNXSV003001807
  • ILMN_1766363
  • PH_hs_0000046
  • TC13000515.hg
  • TC13001385.hg
  • U02687_at
  • g4758395_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • FLT3_HUMAN
  • A0AVG9
  • B7ZLT7
  • B7ZLT8
  • F5H0A0
  • Q13414
sequenceLength 993
species [Species:48887] Homo sapiens
url http://purl.uniprot.org/uniprot/P36888

Referrals

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