Names & Taxonomy

Uniprot ID:
P17948
Entry Name:
VGFR1_HUMAN
Status:
reviewed
Protein Names:
Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase FRT) (Tyrosine-protein kinase receptor FLT) (FLT) (Vascular permeability factor receptor)
Gene Names:
FLT1 FLT FRT VEGFR1
Gene Names Primary:
FLT1
Organism:
Homo sapiens (Human)

Structure

Length:
1338
Sequence:
MVSYWDTGVLLCALLSCLLLTGSSSGSKLKDPELSLKGTQHIMQAGQTLHLQCRGEAAHKWSLPEMVSKESERLSITKSACGRNGKQFCSTLTLNTAQANHTGFYSCKYLAVPTSKKKETESAIYIFISDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVQISTPRPVKLLRGHTLVLNCTATTPLNTRVQMTWSYPDEKNKRASVRRRIDQSNSHANIFYSVLTIDKMQNKDKGLYTCRVRSGPSFKSVNTSVHIYDKAFITVKHRKQQVLETVAGKRSYRLSMKVKAFPSPEVVWLKDGLPATEKSARYLTRGYSLIIKDVTEEDAGNYTILLSIKQSNVFKNLTATLIVNVKPQIYEKAVSSFPDPALYPLGSRQILTCTAYGIPQPTIKWFWHPCNHNHSEARCDFCSNNEESFILDADSNMGNRIESITQRMAIIEGKNKMASTLVVADSRISGIYICIASNKVGTVGRNISFYITDVPNGFHVNLEKMPTEGEDLKLSCTVNKFLYRDVTWILLRTVNNRTMHYSISKQKMAITKEHSITLNLTIMNVSLQDSGTYACRARNVYTGEEILQKKEITIRDQEAPYLLRNLSDHTVAISSSTTLDCHANGVPEPQITWFKNNHKIQQEPGIILGPGSSTLFIERVTEEDEGVYHCKATNQKGSVESSAYLTVQGTSDKSNLELITLTCTCVAATLFWLLLTLFIRKMKRSSSEIKTDYLSIIMDPDEVPLDEQCERLPYDASKWEFARERLKLGKSLGRGAFGKVVQASAFGIKKSPTCRTVAVKMLKEGATASEYKALMTELKILTHIGHHLNVVNLLGACTKQGGPLMVIVEYCKYGNLSNYLKSKRDLFFLNKDAALHMEPKKEKMEPGLEQGKKPRLDSVTSSESFASSGFQEDKSLSDVEEEEDSDGFYKEPITMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNPDYVRKGDTRLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGGSPYPGVQMDEDFCSRLREGMRMRAPEYSTPEIYQIMLDCWHRDPKERPRFAELVEKLGDLLQANVQQDGKDYIPINAILTGNSGFTYSTPAFSEDFFKESISAPKFNSGSSDDVRYVNAFKFMSLERIKTFEELLPNATSMFDDYQGDSSTLLASPMLKRFTWTDSKPKASLKIDLRVTSKSKESGLSDVSRPSFCHSSCGHVSEGKRRFTYDHAELERKIACCSPPPDYNSVVLYSTPPI
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Isoform 1: Cell membrane; Single-pass type I membrane protein. Endosome. Note=Autophosphorylation promotes ubiquitination and endocytosis.; Isoform 2: Secreted

Function

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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
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.
Active Site:
ACT_SITE 1022 1022 Proton acceptor.
Cross Reference Drug Bank:
DB06626 DB09078 DB09079 DB06589 DB08896 DB00398 DB01268
Gene Ontology Go:
endosome
extracellular space
focal adhesion
integral component of plasma membrane
plasma membrane
receptor complex
ATP binding
growth factor binding
placental growth factor-activated receptor activity
transmembrane receptor protein tyrosine kinase activity
vascular endothelial growth factor-activated receptor activity
VEGF-A-activated receptor activity
VEGF-B-activated receptor activity
activation of MAPKK activity
angiogenesis
blood vessel morphogenesis
cell differentiation
cell migration
cellular response to vascular endothelial growth factor stimulus
embryonic morphogenesis
intracellular receptor signaling pathway
monocyte chemotaxis
peptidyl-tyrosine phosphorylation
positive regulation of angiogenesis
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of MAP kinase activity
positive regulation of MAPK cascade
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of phosphatidylinositol 3-kinase signaling
positive regulation of phospholipase C activity
positive regulation of smooth muscle cell proliferation
positive regulation of vascular endothelial growth factor receptor signaling pathway
protein autophosphorylation
regulation of smooth muscle contraction
response to hypoxia
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
vascular endothelial growth factor receptor-1 signaling pathway
Gene Ontology Biological Process:
activation of MAPKK activity
angiogenesis
blood vessel morphogenesis
cell differentiation
cell migration
cellular response to vascular endothelial growth factor stimulus
embryonic morphogenesis
intracellular receptor signaling pathway
monocyte chemotaxis
peptidyl-tyrosine phosphorylation
positive regulation of angiogenesis
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of MAPK cascade
positive regulation of MAP kinase activity
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of phosphatidylinositol 3-kinase signaling
positive regulation of phospholipase C activity
positive regulation of smooth muscle cell proliferation
positive regulation of vascular endothelial growth factor receptor signaling pathway
protein autophosphorylation
regulation of smooth muscle contraction
response to hypoxia
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor-1 signaling pathway
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:
ATP binding
growth factor binding
placental growth factor-activated receptor activity
transmembrane receptor protein tyrosine kinase activity
vascular endothelial growth factor-activated receptor activity
VEGF-A-activated receptor activity
VEGF-B-activated receptor activity
Gene Ontology Cellular Component:
endosome
extracellular space
focal adhesion
integral component of plasma membrane
plasma membrane
receptor complex
Keywords:
3D-structure
ATP-binding
Alternative splicing
Angiogenesis
Cell membrane
Chemotaxis
Complete proteome
Cytoplasm
Developmental protein
Differentiation
Direct protein sequencing
Disulfide bond
Endosome
Glycoprotein
Immunoglobulin domain
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
P22681; P46109; P35222; P08631; P98160; P49763; P27986; P19174; Q05397; Q06124; Q12913; P15692; P15692-4

Publication

PubMed ID:
2158038 8248162 10471394 18593464 18515749 20512933 14702039 15057823 15489334 3040650 9722576 7824266 8605350 9299537 9600074 11141500 11513746 11811792 11312102 14633857 12796773 15001553 15735759 16685275 16286478 18079407 18583712 20551949 21212275 22016384 21752276 17002866 18680722 19230644 19761875 20127948 21711246 21558755 9393862 10543948 14684734 20501651 17344846