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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]
FLT1 (Fms Related Tyrosine Kinase 1) is a Protein Coding gene. Diseases associated with FLT1 include Anal Canal Squamous Cell Carcinoma and Pre-Eclampsia. Among its related pathways are p70S6K Signaling and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is KDR.
Vascular endothelial growth factor is a signaling protein involved in the regulation of angiogenesis and vasculogenesis. VEGF binds to and activates a receptor tyrosine kinase, VEGFR, through transphosphorylation. Three VEGFR isoforms have been identified in humans.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IEA | -- |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | TAS,IBA | 21873635 |
GO:0005021 | vascular endothelial growth factor-activated receptor activity | IMP,IBA | 11312102 |
GO:0005515 | protein binding | IPI | 1312256 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | IEA | -- |
GO:0005615 | extracellular space | TAS | 8248162 |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005768 | endosome | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
|
PPAR Pathway
.66
Rac1 Pathway
.65
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Nuclear Receptor Activation by Vitamin-A
.57
|
2 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
3 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
4 | Nanog in Mammalian ESC Pluripotency |
GSK3 Signaling
.61
Nanog in Mammalian ESC Pluripotency
.61
|
14-3-3 Induced Intracellular Signaling
.59
eNOS Signaling
.48
|
5 | CREB Pathway |
CREB Pathway
.68
IP3 Pathway
.68
|
Activation of PKC through GPCR
.63
Intracellular Calcium Signaling
.50
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001525 | angiogenesis | IEA | -- |
GO:0002040 | sprouting angiogenesis | IBA | 21873635 |
GO:0002548 | monocyte chemotaxis | IDA | 8605350 |
GO:0006468 | protein phosphorylation | IEA | -- |
GO:0006935 | chemotaxis | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Sunitinib | Approved, Investigational | Pharma | Target, inhibitor | VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor, RTK inhibitor, Potent VEGFR, PDGFRbeta and KIT inhibitor, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 540 | |
Pazopanib | Approved | Pharma | Target, inhibitor | VEFGR, c-Kit, and PDGFR inhibitor, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 0 | |
regorafenib | Approved | Pharma | Target, inhibitor | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 0 | |
Axitinib | Approved, Investigational | Pharma | Target, inhibitor, Inhibition | Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 130 | |
Lenvatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 116 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor | 58-64-0 |
|
||
XL 184 |
|
849217-68-1 |
|
|
Compound | Action | Cas Number |
---|---|---|
SU 4312 | Potent inhibitor of VEGFR tyrosine kinase | 5812-07-7 |
SU 5416 | VEGFR inhibitor. Also inhibits KIT, RET, MET and FLT3 | 204005-46-9 |
Sunitinib malate | Potent VEGFR, PDGFRbeta and KIT inhibitor | 341031-54-7 |
XL 184 | Potent VEGFR inhibitor; also inhibits other RTKs | 849217-68-1 |
Compound | Action | Cas Number |
---|---|---|
(E)-FeCP-oxindole | 884338-18-5 | |
(Z)-FeCP-oxindole | 1137967-28-2 | |
Axitinib (AG 013736) | VEGFR1/ c-Kit inhibitor | 319460-85-0 |
BIBF 1120 | VEGFR/PDGF/FGFR inhibitor | 656247-17-5 |
Cabozantinib (XL184, BMS-907351) | VEGFR2/Met/Ret/Kit/FLT//AXL inhibitor | 849217-68-1 |
Cediranib (AZD217) | VEGFR inhibitor receptor,highly potent | 288383-20-0 |
DMH4 | 515880-75-8 | |
Dovitinib (TKI258) Lactate | Oral tyrosine kinase inhibitor (TKI) against FGFR1–3, VEGFR1–3, and platelet-derived growth factor receptor (PDGFR) | 915769-50-5 |
Dovitinib (TKI-258, CHIR-258) | Multitargeted RTK inhibitor | 405169-16-6 |
Dovitinib Dilactic acid | 852433-84-2 | |
Foretinib (GSK1363089) | VEGF and HGF receptor inhibitor | 849217-64-7 |
Fruquintinib(HMPL-013) | Potent and selective inhibitor of VEGFR 1, 2, 3 | 1194506-26-7 |
Ki8751 | VEGFR-2 inhibitor,potent and selective | 228559-41-9 |
KRN 633 | VEGFR inhibitor,ATP-competitive | 286370-15-8 |
Lenvatinib (E7080) | VEGFR inhibitor | 417716-92-8 |
Linifanib (ABT-869) | VEGFR/PDGFR inhibitor | 796967-16-3 |
MGCD-265 | Met/Flt/Flk/Ron/Tie-2 inhibitor | 875337-44-3 |
Motesanib Diphosphate (AMG-706) | VEGFR/ PDGFR/c-Kit/Ret inhibitor | 857876-30-3 |
OSI-930 | Inhibitor of Kit, KDR, Flt, CSF-1R, c-Raf and Lck | 728033-96-3 |
Pazopanib (GW-786034) | VEGFR/PDGFR/FGFR inhibitor | 635702-64-6 |
Pazopanib Hydrochloride | VEGFR/PDGFR/FGFR/c-Kit/ c-Fms inhibitor | 635702-64-6 |
PD 173074 | FGFR inhibitor | 219580-11-7 |
SKLB610 | Potent VEGFR inhibitor | 1125780-41-7 |
SU 4312 | 5812-07-7 | |
Sunitinib | RTK inhibitor | 557795-19-4 |
Sunitinib malate | VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor | 341031-54-7 |
Tivozanib (AV-951) | VEGFR inhibitor,potent and selective | 475108-18-0 |
Vatalanib | VEGFR-1/-2 inhibitor,cell-permeable | 212141-54-3 |
Vatalanib (PTK787) 2HCl | Tyrosine kinase receptor inhibitor | 212141-51-0 |
ZM 306416 | VEGFR (Flt and KDR) inhibitor | 690206-97-4 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
chimpanzee (Pan troglodytes) |
Mammalia | FLT1 33 32 |
|
OneToOne | |
dog (Canis familiaris) |
Mammalia | FLT1 33 32 |
|
OneToOne | |
cow (Bos Taurus) |
Mammalia | FLT1 33 32 |
|
OneToOne | |
oppossum (Monodelphis domestica) |
Mammalia | FLT1 33 |
|
OneToOne | |
mouse (Mus musculus) |
Mammalia | Flt1 17 33 32 |
|
||
platypus (Ornithorhynchus anatinus) |
Mammalia | FLT1 33 |
|
OneToOne | |
chicken (Gallus gallus) |
Aves | FLT1 33 32 |
|
OneToOne | |
lizard (Anolis carolinensis) |
Reptilia | FLT1 33 |
|
OneToOne | |
zebrafish (Danio rerio) |
Actinopterygii | flt1 33 32 |
|
OneToOne | |
-- 32 |
|
||||
fruit fly (Drosophila melanogaster) |
Insecta | tor 34 |
|
|
|
CG3277 34 |
|
|
|||
Cad96Ca 33 |
|
ManyToMany | |||
Pvr 33 |
|
ManyToMany | |||
worm (Caenorhabditis elegans) |
Secernentea | Y50D4B.6 34 |
|
|
|
kin-16 34 |
|
|
|||
R09D1.12 34 |
|
|
|||
ver-2 34 |
|
|
|||
ver-3 34 |
|
|
|||
sea squirt (Ciona savignyi) |
Ascidiacea | -- 33 |
|
OneToMany | |
Cin.3210 32 |
|
||||
sea squirt (Ciona intestinalis) |
Ascidiacea | Cin.3210 32 |
|
SNP ID | Clin | Chr 13 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs148695719 | not-provided, Carcinoma of colon | 28,322,872(-) | T/A | coding_sequence_variant, genic_downstream_transcript_variant, synonymous_variant | |
rs2296189 | not-provided, Carcinoma of colon | 28,319,505(-) | A/C/G | coding_sequence_variant, genic_downstream_transcript_variant, synonymous_variant | |
rs537105078 | not-provided, Carcinoma of colon | 28,327,589(-) | C/G | genic_downstream_transcript_variant, intron_variant | |
rs537403174 | not-provided, Carcinoma of colon | 28,317,613(-) | T/G | genic_downstream_transcript_variant, intron_variant | |
rs553261958 | A glioma low grade oligodendroglioma sample | 28,345,458(-) | C/T | coding_sequence_variant, genic_downstream_transcript_variant, missense_variant |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv3388394 | CNV | duplication | 20981092 |
esv34052 | CNV | loss | 18971310 |
esv3412790 | CNV | duplication | 20981092 |
esv3550237 | CNV | deletion | 23714750 |
nsv455850 | CNV | loss | 19166990 |
nsv561389 | CNV | loss | 21841781 |