KDR

Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]

Kinase Insert Domain Receptor

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.

AngiogenesisManual Assertion Based On ExperimentIBA:GO_Central
Branching involved in blood vessel morphogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Calcium ion homeostasisIEA:Ensembl
Calcium-mediated signaling using intracellular calcium sourceManual Assertion Based On ExperimentIMP:UniProtKB
Cell fate commitmentIEA:Ensembl
Cell maturationIEA:Ensembl
Cell migrationManual Assertion Based On ExperimentIBA:GO_Central
Cell migration involved in sprouting angiogenesisISS:BHF-UCL
Cellular response to hydrogen sulfideManual Assertion Based On ExperimentIDA:BHF-UCL
Cellular response to vascular endothelial growth factor stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Embryonic hemopoiesisISS:UniProtKB
Endocardium developmentIEA:Ensembl
Endothelial cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Endothelium developmentISS:UniProtKB
ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:BHF-UCL
Hematopoietic progenitor cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Lung alveolus developmentIEA:Ensembl
Lymph vessel developmentIEA:Ensembl
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of endothelial cell apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of gene expressionManual Assertion Based On ExperimentIDA:BHF-UCL
Ovarian follicle developmentIEA:Ensembl
Peptidyl-tyrosine autophosphorylationISS:BHF-UCL
Peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of angiogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of blood vessel endothelial cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of BMP signaling pathwayIEA:Ensembl
Positive regulation of cell migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cell migration involved in sprouting angiogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of endothelial cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of endothelial cell proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of focal adhesion assemblyManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of kinase activityManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of macroautophagyManual Assertion Based On ExperimentIGI:MGI
Positive regulation of MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of mesenchymal cell proliferationIEA:Ensembl
Positive regulation of mitochondrial depolarizationManual Assertion Based On ExperimentIGI:MGI
Positive regulation of mitochondrial fissionManual Assertion Based On ExperimentIGI:MGI
Positive regulation of nitric-oxide synthase biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of positive chemotaxisManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of vasculogenesisISS:UniProtKB
Post-embryonic camera-type eye morphogenesisIEA:Ensembl
Protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein kinase B signalingManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of bone developmentIEA:Ensembl
Regulation of cell shapeManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of hematopoietic progenitor cell differentiationIEA:Ensembl
Surfactant homeostasisIEA:Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Vascular endothelial growth factor receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Vascular endothelial growth factor receptor-2 signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Vascular endothelial growth factor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Vascular wound healingManual Assertion Based On ExperimentIMP:BHF-UCL
VasculogenesisISS:UniProtKB

Cell junction; Endoplasmic reticulum; Cell membrane. Localized with RAP1A at cell-cell junctions (By similarity).
Colocalizes with ERN1 and XBP1 in the endoplasmic reticulum in endothelial cells in a vascular endothelial growth factor (VEGF)-dependent manner (PubMed:23529610).
Isoform 1: Cell membrane; Cytoplasm; Nucleus; Cytoplasmic vesicle; Early endosome. 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.
Isoform 2&3: Secreted

Hemangioma, capillary infantile (HCI):
A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring.
Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.

Extracellular: 20-764
Helical: 765-785
Cytoplasmic: 786-1356

N-glycosylated.
Ubiquitinated. Tyrosine phosphorylation of the receptor promotes its poly-ubiquitination, leading to its degradation via the proteasome or lysosomal proteases.
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-951 is important for interaction with SH2D2A/TSAD and VEGFA-mediated reorganization of the actin cytoskeleton. Phosphorylation at Tyr-1175 is important for interaction with PLCG1 and SHB. Phosphorylation at Tyr-1214 is important for interaction with NCK1 and FYN. Dephosphorylated by PTPRB. Dephosphorylated by PTPRJ at Tyr-951, Tyr-996, Tyr-1054, Tyr-1059, Tyr-1175 and Tyr-1214.
The inhibitory disulfide bond between Cys-1024 and Cys-1045 may serve as a specific molecular switch for H(2)S-induced modification that regulates KDR/VEGFR2 function.