Names & Taxonomy

Uniprot ID:
P35968
Entry Name:
VGFR2_HUMAN
Status:
reviewed
Protein Names:
Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor) (KDR) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309)
Gene Names:
KDR FLK1 VEGFR2
Gene Names Primary:
KDR
Organism:
Homo sapiens (Human)

Structure

Length:
1356
Sequence:
MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLDWLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQDYRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWDSKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPPEIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVPPQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPYPCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGERVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPTPVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLTVLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNRNLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWLLLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLKRRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVSCMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDSGMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYSSEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell junction

Function

Function:
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.
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, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by the small molecule PTK inhibitor SU5614 ((3Z)-5-Chloro-3--1,3-dihydro-2H-indol-2-one). May be regulated by hydrogen sulfide (H(2)S) levels via a H(2)S-sensitive intracellular disulfide bond.
Active Site:
ACT_SITE 1028 1028 Proton acceptor.
Cross Reference Drug Bank:
DB06626 DB08875 DB09078 DB09079 DB06589 DB08901 DB05578 DB08896 DB00398 DB01268
Gene Ontology Go:
cell junction
cytoplasmic, membrane-bounded vesicle
early endosome
endoplasmic reticulum
endosome
extracellular region
Golgi apparatus
integral component of plasma membrane
membrane raft
nucleus
plasma membrane
sorting endosome
ATP binding
growth factor binding
Hsp90 protein binding
integrin binding
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
vascular endothelial growth factor binding
vascular endothelial growth factor-activated receptor activity
angiogenesis
calcium-mediated signaling using intracellular calcium source
cell migration involved in sprouting angiogenesis
cellular response to vascular endothelial growth factor stimulus
embryonic hemopoiesis
endothelium development
extracellular matrix organization
negative regulation of apoptotic process
negative regulation of endothelial cell apoptotic process
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
positive regulation of angiogenesis
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway
positive regulation of endothelial cell migration
positive regulation of endothelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of focal adhesion assembly
positive regulation of macroautophagy
positive regulation of MAPK cascade
positive regulation of mitochondrial depolarization
positive regulation of mitochondrial fission
positive regulation of nitric-oxide synthase biosynthetic process
positive regulation of phosphatidylinositol 3-kinase signaling
positive regulation of positive chemotaxis
positive regulation of protein phosphorylation
positive regulation of vasculogenesis
protein autophosphorylation
regulation of cell shape
signal transduction by protein phosphorylation
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
vasculogenesis
viral process
Gene Ontology Biological Process:
angiogenesis
calcium-mediated signaling using intracellular calcium source
cell migration involved in sprouting angiogenesis
cellular response to vascular endothelial growth factor stimulus
embryonic hemopoiesis
endothelium development
extracellular matrix organization
negative regulation of apoptotic process
negative regulation of endothelial cell apoptotic process
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
positive regulation of angiogenesis
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway
positive regulation of endothelial cell migration
positive regulation of endothelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of focal adhesion assembly
positive regulation of macroautophagy
positive regulation of MAPK cascade
positive regulation of mitochondrial depolarization
positive regulation of mitochondrial fission
positive regulation of nitric-oxide synthase biosynthetic process
positive regulation of phosphatidylinositol 3-kinase signaling
positive regulation of positive chemotaxis
positive regulation of protein phosphorylation
positive regulation of vasculogenesis
protein autophosphorylation
regulation of cell shape
signal transduction by protein phosphorylation
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
vasculogenesis
viral process
Gene Ontology Molecular Function:
ATP binding
growth factor binding
Hsp90 protein binding
integrin binding
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
vascular endothelial growth factor-activated receptor activity
vascular endothelial growth factor binding
Gene Ontology Cellular Component:
cell junction
cytoplasmic, membrane-bounded vesicle
early endosome
endoplasmic reticulum
endosome
extracellular region
Golgi apparatus
integral component of plasma membrane
membrane raft
nucleus
plasma membrane
sorting endosome
Keywords:
3D-structure
ATP-binding
Alternative splicing
Angiogenesis
Cell junction
Cell membrane
Complete proteome
Cytoplasm
Cytoplasmic vesicle
Developmental protein
Differentiation
Disulfide bond
Endoplasmic reticulum
Endosome
Glycoprotein
Host-virus interaction
Immunoglobulin domain
Kinase
Membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
P46108; P35916; O60565; P98160; P17301; P09382; P08581; P16333; O14786; O75340; Q12913; P12931; P15692; P15692-4

Publication

PubMed ID:
18593464 19668192 15815621 15489334 1656371 7559454 1417831 7929439 9160888 9837777 9804796 10600473 10037737 10102632 10590123 11387210 12649282 12881528 15026417 14991896 15215251 15962004 16966330 17004325 17303569 19033661 19136612 18936167 19834490 20179233 20224550 21539813 20705758 17002866 17658244 18680722 19230644 19761875 20462514 21779435 21711246 21406692 21893193 23199280 23529610 10368301 15837294 17253678 18529047 20080685 20145116 21827946 11807987 16959974 17344846 18931684