| Comment type | Description |
|---|
| Catalytic Activity | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- ProRule:PRU10028}. |
| Developmental Stage | Increases during pregnancy (1.6-fold at 4 days) and lactation (3.8-fold at 7 days). Decreases in the early phases of involution (45%, 50% and 34% on days 1, 2, and 3 respectively) |
| Domain | The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding |
| 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. May be regulated by hydrogen sulfide (H(2)S) levels via a sensitive intracellular disulfide bond (By similarity) |
| 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 may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. 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 (By similarity) |
| Ptm | Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-947 is important for interaction with SH2D2A/TSAD and VEGFA-mediated reorganization of the actin cytoskeleton. Phosphorylation at Tyr-1171 is important for interaction with PLCG1 and SHB. Phosphorylation at Tyr-1210 is important for interaction with NCK1 and FYN. Dephosphorylated by PTPRB. Dephosphorylated by PTPRJ at Tyr-797, Tyr-947, Tyr-992, Tyr-1050, Tyr-1055, Tyr-1171 and Tyr-1210 (By similarity) |
| Ptm | N-glycosylated |
| Ptm | The inhibitory disulfide bond between Cys-1020 and Cys-1041 may serve as a specific molecular switch for H(2)S-induced modification that regulates VEGFR2 function |
| Ptm | Ubiquitinated. Tyrosine phosphorylation of the receptor promotes its poly-ubiquitination, leading to its degradation via the proteasome or lysosomal proteases (By similarity) |
| Similarity | Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily |
| Similarity | Contains 1 protein kinase domain |
| Similarity | Contains 7 Ig-like C2-type (immunoglobulin-like) domains |
| Subcellular Location | Cell membrane ; Single-pass type I membrane protein {ECO:0000250}. Cytoplasm . Nucleus {ECO:0000250}. Cytoplasmic vesicle . Early endosome {ECO:0000250}. Cell junction . Note=Detected on caveolae-enriched lipid rafts at the cell surface. Is recycled from the plasma membrane to endosomes and back again. Phosphorylation triggered by VEGFA binding promotes internalization and subsequent degradation. VEGFA binding triggers internalization and translocation to the nucleus. Localized with RAP1A at cell-cell junctions (By similarity) |
| Subunit | Homodimer in the presence of bound dimeric VEGFA, VEGFC or VEGFD ligands; monomeric in the absence of bound ligands. Can also form heterodimers with FLT1/VEGFR1 and FLT4/VEGFR2. Interacts (tyrosine phosphorylated) with LFYN, NCK1, PLCG1. Interacts (tyrosine-phosphorylated active form preferentially) with DAB2IP (via C2 domain and active form preferentially); the interaction occurs at the late phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts with SHBSH2D2A/TSAD, GRB2, MYOF, CBL and PDCD6 (By similarity) |
| Tissue Specificity | Expressed in the post-pubertal mammary glands |