Seroatlas · Human Serome Atlas

FLT3

Receptor-type tyrosine-protein kinase FLT3

Also known as: CD135, FLK2, FLT3_HUMAN, STK1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P36888
Gene: FLT3
Ensembl: ENSG00000122025
Chromosome: 13
Canonical length: 993 aa
Protein class: Cancer-related genes, CD markers, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Predicted membrane proteins, RAS pathway related proteins
Subcellular location: Endoplasmic reticulum
Quaternary structure: Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

993 residues, UniProt reviewed canonical sequence.

>P36888|FLT3
     1  MPALARDGGQ LPLLVVFSAM IFGTITNQDL PVIKCVLINH KNNDSSVGKS SSYPMVSESP
    61  EDLGCALRPQ SSGTVYEAAA VEVDVSASIT LQVLVDAPGN ISCLWVFKHS SLNCQPHFDL
   121  QNRGVVSMVI LKMTETQAGE YLLFIQSEAT NYTILFTVSI RNTLLYTLRR PYFRKMENQD
   181  ALVCISESVP EPIVEWVLCD SQGESCKEES PAVVKKEEKV LHELFGTDIR CCARNELGRE
   241  CTRLFTIDLN QTPQTTLPQL FLKVGEPLWI RCKAVHVNHG FGLTWELENK ALEEGNYFEM
   301  STYSTNRTMI RILFAFVSSV ARNDTGYYTC SSSKHPSQSA LVTIVEKGFI NATNSSEDYE
   361  IDQYEEFCFS VRFKAYPQIR CTWTFSRKSF PCEQKGLDNG YSISKFCNHK HQPGEYIFHA
   421  ENDDAQFTKM FTLNIRRKPQ VLAEASASQA SCFSDGYPLP SWTWKKCSDK SPNCTEEITE
   481  GVWNRKANRK VFGQWVSSST LNMSEAIKGF LVKCCAYNSL GTSCETILLN SPGPFPFIQD
   541  NISFYATIGV CLLFIVVLTL LICHKYKKQF RYESQLQMVQ VTGSSDNEYF YVDFREYEYD
   601  LKWEFPRENL EFGKVLGSGA FGKVMNATAY GISKTGVSIQ VAVKMLKEKA DSSEREALMS
   661  ELKMMTQLGS HENIVNLLGA CTLSGPIYLI FEYCCYGDLL NYLRSKREKF HRTWTEIFKE
   721  HNFSFYPTFQ SHPNSSMPGS REVQIHPDSD QISGLHGNSF HSEDEIEYEN QKRLEEEEDL
   781  NVLTFEDLLC FAYQVAKGME FLEFKSCVHR DLAARNVLVT HGKVVKICDF GLARDIMSDS
   841  NYVVRGNARL PVKWMAPESL FEGIYTIKSD VWSYGILLWE IFSLGVNPYP GIPVDANFYK
   901  LIQNGFKMDQ PFYATEEIYI IMQSCWAFDS RKRPSFPNLT SFLGCQLADA EEAMYQNVDG
   961  RVSECPHTYQ NRRPFSREMD LGLLSPQAQV EDS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FLT3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 1
Mean surface accessibility (rSASA): 0.34
Highest tissue expression: 8.9 nTPM

Expression across tissuesHPA

Tissue

cerebellum: 8.9 nTPM
lymph node: 6.1 nTPM
spleen: 5.3 nTPM
bone marrow: 5 nTPM
thymus: 4.3 nTPM
tonsil: 3.4 nTPM

Single-cell type

hematopoietic stem cells: 850 nCPM
thymocytes: 597 nCPM
monocyte progenitors: 515 nCPM
cdc: 332 nCPM
monocytes: 176 nCPM
pdcs: 173 nCPM

Immune cell

myeloid DC: 69 nTPM
plasmacytoid DC: 26 nTPM
classical monocyte: 3.6 nTPM
eosinophil: 3.4 nTPM
total PBMC: 2.7 nTPM
basophil: 2.4 nTPM

Brain region

cerebellum: 11 nTPM
pons: 3.9 nTPM
medulla oblongata: 2.8 nTPM
cerebral cortex: 2 nTPM
spinal cord: 2 nTPM
white matter: 2 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FLT3.

Disease | AllUniProt

Conditions FLT3 is implicated in, by any mechanism.

Leukemia, acute myelogenous (AML) MIM:601626

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 242 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.35
gnomAD pLI: 0.61
gnomAD missense Z: 0.98
DepMap mean gene effect: -0.14
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of FLT3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads FLT3 as an antibody target. Whether an autoantibody or antibody against FLT3 could matter depends on whether native FLT3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

FLT3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label FLT3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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