Browse FLT1

Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Isoform 1: Cell membrane; Single-pass type I membrane protein. Endosome. Note=Autophosphorylation promotes ubiquitination and endocytosis.; SUBCELLULAR LOCATION: Isoform 2: Secreted ; SUBCELLULAR LOCATION: Isoform 3: Secreted.; SUBCELLULAR LOCATION: Isoform 4: Secreted.; SUBCELLULAR LOCATION: Isoform 5: Cytoplasm ; SUBCELLULAR LOCATION: Isoform 6: Cytoplasm ; SUBCELLULAR LOCATION: Isoform 7: Cytoplasm
Domain PF07679 Immunoglobulin I-set domain
PF00047 Immunoglobulin domain
PF07714 Protein tyrosine kinase
Function

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.

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0002548 monocyte chemotaxis
GO:0006644 phospholipid metabolic process
GO:0010517 regulation of phospholipase activity
GO:0010518 positive regulation of phospholipase activity
GO:0010863 positive regulation of phospholipase C activity
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0019216 regulation of lipid metabolic process
GO:0030335 positive regulation of cell migration
GO:0030595 leukocyte chemotaxis
GO:0030947 regulation of vascular endothelial growth factor receptor signaling pathway
GO:0030949 positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0033674 positive regulation of kinase activity
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0036323 vascular endothelial growth factor receptor-1 signaling pathway
GO:0038084 vascular endothelial growth factor signaling pathway
GO:0040017 positive regulation of locomotion
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043550 regulation of lipid kinase activity
GO:0043551 regulation of phosphatidylinositol 3-kinase activity
GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity
GO:0045765 regulation of angiogenesis
GO:0045766 positive regulation of angiogenesis
GO:0045834 positive regulation of lipid metabolic process
GO:0045860 positive regulation of protein kinase activity
GO:0046777 protein autophosphorylation
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0048514 blood vessel morphogenesis
GO:0050900 leukocyte migration
GO:0051272 positive regulation of cellular component movement
GO:0060191 regulation of lipase activity
GO:0060193 positive regulation of lipase activity
GO:0060326 cell chemotaxis
GO:0071674 mononuclear cell migration
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090218 positive regulation of lipid kinase activity
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0097529 myeloid leukocyte migration
GO:1900274 regulation of phospholipase C activity
GO:1901342 regulation of vasculature development
GO:1903725 regulation of phospholipid metabolic process
GO:1903727 positive regulation of phospholipid metabolic process
GO:1904018 positive regulation of vasculature development
GO:2000147 positive regulation of cell motility
Molecular Function GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005021 vascular endothelial growth factor-activated receptor activity
GO:0019199 transmembrane receptor protein kinase activity
GO:0019838 growth factor binding
GO:0036326 VEGF-A-activated receptor activity
GO:0036327 VEGF-B-activated receptor activity
GO:0036332 placental growth factor-activated receptor activity
Cellular Component GO:0005924 cell-substrate adherens junction
GO:0005925 focal adhesion
GO:0030055 cell-substrate junction
GO:0043235 receptor complex
> KEGG and Reactome Pathway
 
KEGG hsa04014 Ras signaling pathway
hsa04015 Rap1 signaling pathway
hsa04060 Cytokine-cytokine receptor interaction
hsa04066 HIF-1 signaling pathway
hsa04144 Endocytosis
hsa04151 PI3K-Akt signaling pathway
hsa04510 Focal adhesion
Reactome R-HSA-194306: Neurophilin interactions with VEGF and VEGFR
R-HSA-162582: Signal Transduction
R-HSA-194138: Signaling by VEGF
R-HSA-195399: VEGF binds to VEGFR leading to receptor dimerization
R-HSA-194313: VEGF ligand-receptor interactions
Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between FLT1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between FLT1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
18337760Kidney CarcinomaPromote immunitySorafenib, a novel drug for metastatic renal cancer, has broad-spectrum activity against multiple tyrosine kinases, including Raf-1, vascular endothelial growth factor receptor and platelet-derived growth factor receptor. These findings suggest that sorafenib may cause the loss of T-cell immune response by inducing apoptosis and targeting LCK. This could potentially lead to immunosuppression in patients with cancer.
23447383Chronic Lymphocytic LeukemiaInhibit immunity (T cell function)In our study, we characterized mRNA levels of VEGF receptors including NRP1 in a large cohort of CLL patients (n = 114), additionally we performed a detailed characterization of NRP1 expression on B cells, plasmacytoid dendritic cells (PDCs) and regulatory T cells (Tregs). The expression of NRP1 was significantly higher on leukemic lymphocytes compared to control B lymphocytes on mRNA and protein levels (22.72% vs. 0.2%, p = 0.0003, respectively), Tregs (42.6% vs. 16.05%, p = 0.0003) and PDCs (100% vs. 98% p < 0.0001). In functional studies, we found higher NRP1 expression on CLL cells after stimulation with VEGF. The correlation between expression of VEGF receptors: FLT1, NRP1 and FOXP3 expression (r(2) = 0.53, p < 0.0001 and r(2) = 0.49, p < 0.0001, respectively) was observed.
21209070Colon CarcinomaPromote immunity (T cell function)Antagonism of VEGF by genetically engineered dendritic cells is essential to induce antitumor immunity against malignant ascites. Using a murine model of MA with CT26 colon cancer cells, we here determined that the imbalance between the VEGF-A/vascular permeability factor and its decoy receptor, soluble fms-like tryrosine kinase receptor-1 (sFLT-1), was a major cause of MA resistance to dendritic cell (DC)-based immunotherapy. These findings were not seen in immunodeficient mice, indicating that a VEGF-A/sFLT-1 imbalance is critical for determining the antitumor immune response by DC-vaccination therapy against MA.
18566400Renal Cell CarcinomaInhibit immunityOxidative stress regulates expression of VEGFR1 in myeloid cells: link to tumor-induced immune suppression in renal cell carcinoma. Data suggest that tumor-induced oxidative stress may promote both VEGFR1 up-regulation and immunosuppressive function in bone marrow-derived myeloid cells.
Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of FLT1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of FLT1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.8110.0275
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.9510.439
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.710.452
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1720.527
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.2750.896
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.0470.985
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1990.67
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4360.78
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.020.99
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.8490.557
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 282.3870.21
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.150.154
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of FLT1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.45.51.90.66
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.45.12.30.647
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211714.329.4-15.10.426
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.516.7-4.21
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.436.4-210.357
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91622.2022.20.12
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 382715.83.712.10.224
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.17.71.41
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1614250250.103
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FLT1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FLT1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FLT1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FLT1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of FLT1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between FLT1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolFLT1
Namefms-related tyrosine kinase 1
Aliases VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting FLT1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting FLT1.
ID Name Drug Type Targets #Targets
DB00398SorafenibSmall MoleculeBRAF, FGFR1, FLT1, FLT3, FLT4, KDR, KIT, PDGFRB, RAF1, RET10
DB01268SunitinibSmall MoleculeCSF1R, FLT1, FLT3, FLT4, KDR, KIT, PDGFRA, PDGFRB8
DB04879VatalanibSmall MoleculeFLT1, FLT4, KDR3
DB05075TG-100801Small MoleculeCSK, FLT1, FLT4, KDR4
DB05913OSI-930Small MoleculeFLT1, KIT2
DB05932DenibulinSmall MoleculeFLT1, FLT4, VEGFA3
DB06080ABT-869Small MoleculeCSF1R, FLT1, FLT3, FLT4, KDR, KIT6
DB06101IMC-1C11BiotechFLT1, FLT4, KDR3
DB06589PazopanibSmall MoleculeFGF1, FGFR3, FLT1, FLT4, ITK, KDR, KIT, PDGFRA, PDGFRB, SH2B310
DB06626AxitinibSmall MoleculeFLT1, FLT4, KDR3
DB07288N-(4-chlorophenyl)-2-[(pyridin-4-ylmethyl)amino]benzamideSmall MoleculeFLT11
DB08896RegorafenibSmall MoleculeABL1, BRAF, DDR2, EPHA2, FGFR1, FGFR2, FLT1, FLT4, FRK, KDR, KIT, ......18
DB09078LenvatinibSmall MoleculeFGFR1, FGFR2, FGFR3, FGFR4, FLT1, FLT4, KDR, KIT8
DB09079NintedanibSmall MoleculeFGFR1, FGFR2, FGFR3, FLT1, FLT3, FLT4, KDR, LCK, LYN, SRC10
DB09221PolaprezincSmall MoleculeFLT1, HSP90AA1, HSP90AB1, IL3, IL6, NGF, PDGFRB, TNF8