Tclin FLT1 Vascular endothelial growth factor receptor 1

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• P17948
• A3E342
• A3E344
• A8KA71
• B0LPF1
• B2BF46
• B2BF47
• B2BF48
• B3FR89
• B5A923
• F5H5L6
• O60722
• P16057
• Q12954
• VEGFR-1

Gene Name

• FLT1

Ensembl ID

• ENST00000282397
• ENSP00000282397
• ENSG00000102755
• ENST00000539099
• ENSP00000442630
• ENST00000541932
• ENSP00000437631
• ENST00000543394
• ENSP00000437841
• ENST00000615840
• ENSP00000484039

Symbol

• FLT
• FRT
• VEGFR1
• FLT
• FLT-1
• VEGFR1
• VEGFR-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
PubMedID	1
molecular function	0.99
biological process	0.94
trait	0.93

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Vegfr Family / Vascular Endothelial Growth Factor Receptor 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2334.76   (req: < 5)

Gene RIFs: 714   (req: <= 3)

Antibodies: 1445   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2334.76   (req: >= 5)

Gene RIFs: 714   (req: > 3)

Antibodies: 1445   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 33

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 316

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 12