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FLT1 (Fms related tyrosine kinase 1)

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Summary of FLT1

This gene encodes a protein that works as a cell surface receptor. It can cause cancer and tumor proliferation (R).

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The Function of FLT1

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.

Protein names

Recommended name:

Vascular endothelial growth factor receptor 1

Short name:

FLT

Alternative name(s):

VEGFR-1
Fms-like tyrosine kinase 1
FLT-1
Tyrosine-protein kinase FRT
Tyrosine-protein kinase receptor FLT
Vascular permeability factor receptor

FLT1 SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS17086609 (FLT1) ??
  2. RS9508025 (FLT1) ??

Top Gene-Substance Interactions

FLT1 Interacts with These Diseases

Disease Score

Substances That Increase FLT1

Substances Interaction Organism Category

Substances That Decrease FLT1

Substances Interaction Organism Category

Advanced Summary

     From UniProt: Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.

     From NCBI Gene: This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. The soluble isoforms are associated with the onset of pre-eclampsia.[provided by RefSeq, May 2009] From UniProt: Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • Arnt
  • p53
  • AP-1
  • c-Jun
  • NF-kappaB1
  • NF-kappaB
  • STAT1

Tissue specificity:

Detected in normal lung, but also in placenta, liver, kidney, heart and brain tissues. Specifically expressed in most of the vascular endothelial cells, and also expressed in peripheral blood monocytes. Isoform 2 is strongly expressed in placenta. Isoform 3 is expressed in corneal epithelial cells (at protein level). Isoform 3 is expressed in vascular smooth muscle cells (VSMC).

Gene Pathways:

  • Rheumatoid arthritis
  • Signal Transduction
  • Cytokine-cytokine receptor interaction

Induction:

Up-regulated in coculture of VSMC/endothelial cell (EC) or by direct exposure to VEGF of VSMC monoculture. Up-regulated from the second trimester of pregnancy to the term and in the placenta of women with preeclampsia (PE). Up-regulated in monocytes exposed to bacterial lipopolysaccharide (LPS).

Enzyme Regulation:

Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFB or PGF leads to dimerization and activation by autophosphorylation on tyrosine residues.

Molecular Function:

  • Transmembrane Receptor Protein Tyrosine Kinase Activity
  • Vascular Endothelial Growth Factor-Activated Receptor Activity
  • Atp Binding
  • Growth Factor Binding
  • Vegf-A-Activated Receptor Activity
  • Vegf-B-Activated Receptor Activity
  • Placental Growth Factor-Activated Receptor Activity

Biological Processes:

  • Activation Of Mapkk Activity
  • Angiogenesis
  • Response To Hypoxia
  • Monocyte Chemotaxis
  • Regulation Of Smooth Muscle Contraction
  • Transmembrane Receptor Protein Tyrosine Kinase Signaling Pathway
  • Positive Regulation Of Cell Proliferation
  • Positive Regulation Of Phospholipase C Activity
  • Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
  • Peptidyl-Tyrosine Phosphorylation
  • Cell Differentiation
  • Positive Regulation Of Cell Migration
  • Intracellular Receptor Signaling Pathway
  • Positive Regulation Of Vascular Endothelial Growth Factor Receptor Signaling Pathway
  • Cellular Response To Vascular Endothelial Growth Factor Stimulus
  • Vascular Endothelial Growth Factor Receptor-1 Signaling Pathway
  • Positive Regulation Of Map Kinase Activity
  • Positive Regulation Of Mapk Cascade
  • Positive Regulation Of Phosphatidylinositol 3-Kinase Activity
  • Positive Regulation Of Angiogenesis
  • Protein Autophosphorylation
  • Vascular Endothelial Growth Factor Receptor Signaling Pathway
  • Blood Vessel Morphogenesis
  • Embryonic Morphogenesis
  • Positive Regulation Of Smooth Muscle Cell Proliferation

Drug Bank:

  • Lenvatinib
  • Nintedanib
  • Pazopanib
  • Sorafenib
  • Sunitinib
  • Axitinib
  • Regorafenib
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| A306_11818| AS27_03128| ascular endothelial growth factor/vascular permeability factor receptor| CB1_001907068| D623_10026431| EGK_09204| embryonic receptor kinase 2| FLT| FLT-1| flt1a| flt1b| flt-1 type VEGF receptor| flt-receptor| flt-type VEGF receptor| fms-like tyrosine kinase 1| fms-like-tyrosine kinase 1| fms-related tyrosine kinase 1| fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)| H920_05237| I79_002099| M91_03506| M959_06277| N300_09456| N301_16566| N302_00902| N303_02111| N305_11034| N306_02355| N307_02345| N308_01847| N320_05398| N326_13447| N333_06155| N334_13376| N335_03412| N336_01726| PAL_GLEAN10006825| PANDA_016110| receptor tyrosine kinase Flt1b| sFlt1| soluble fms-like tyrosine kinase 1| soluble VEGF receptor 1| TREES_T100016457| tyrosine-protein kinase FRT| tyrosine-protein kinase receptor FLT| UY3_05209| vascular endothelial growth factor 1| Vascular endothelial growth factor receptor 1| vascular endothelial growth factor receptor 1-like| vascular endothelial growth factor/vascular permeability factor receptor| vascular permeability factor receptor| VEGFR1| VEGFR-1| VEGF-receptor| VEGF receptor flt| Y1Q_023545| Y956_13466| Z169_06386| flt1

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