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  3. KDR

KDR (Kinase insert domain receptor)

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Summary of KDR

This gene encodes one of the two receptors of the VEGF and helps look over cells' survival, migration, and sprouting. It is associated with tumor growth (R). 

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The Function of KDR

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.

Protein names

Recommended name:

Vascular endothelial growth factor receptor 2

Short name:

KDR

Alternative name(s):

VEGFR-2
Fetal liver kinase 1
FLK-1
Kinase insert domain receptor
Protein-tyrosine kinase receptor flk-1
CD antigen CD309

KDR SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS11941492 (KDR) ??
  2. RS1531289 (KDR) ??
  3. RS2071559 (KDR) ??
  4. RS2305948 (KDR) ??
  5. RS2305949 (KDR) ??
  6. RS34231037 (KDR) ??
  7. RS7667298 (KDR) ??

Top Gene-Substance Interactions

KDR Interacts with These Diseases

Disease Score

Substances That Increase KDR

Substances Interaction Organism Category

Substances That Decrease KDR

Substances Interaction Organism Category

Advanced Summary

     From NCBI Gene: Hemangioma, capillary infantileFrom UniProt: 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. [MIM:602089] 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.

     From NCBI Gene: 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] From UniProt: 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.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • p53
  • STAT3
  • Sp1
  • GATA-1
  • Tal-1beta
  • AML1a
  • GATA-2
  • Tal-1

Tissue specificity:

Detected in cornea (at protein level). Widely expressed.

Gene Pathways:

  • Signal Transduction
  • Cytokine-cytokine receptor interaction
  • Extracellular matrix organization
  • VEGF signaling pathway

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-[(3,5-dimethyl-1H-pyrrol-2-yl)methylene]-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.

Molecular Function:

  • Atp Binding
  • Growth Factor Binding
  • Hsp90 Protein Binding
  • Integrin Binding
  • Protein Tyrosine Kinase Activity
  • Signal Transducer, Downstream Of Receptor, With Protein Tyrosine Kinase Activity
  • Transmembrane Receptor Protein Tyrosine Kinase Activity
  • Vascular Endothelial Growth Factor-Activated Receptor Activity
  • Vascular Endothelial Growth Factor Binding

Biological Processes:

  • 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
  • Transmembrane Receptor Protein Tyrosine Kinase Signaling Pathway
  • Vascular Endothelial Growth Factor Receptor Signaling Pathway
  • Vasculogenesis
  • Viral Process

Drug Bank:

  • Ramucirumab
  • Cabozantinib
  • Lenvatinib
  • Nintedanib
  • Pazopanib
  • Ponatinib
  • Sorafenib
  • Sunitinib
  • Axitinib
  • Regorafenib
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| protein-tyrosine kinase| 6130401C07| A306_08933| AS27_13353| AS28_04941| CB1_000310012| CD309| fetal liver kinase| fetal liver kinase 1| fetal liver kinase-1| fetal liver kinase 1b| FLK| flk1| flk-1| flk1b| FLK-1b| FLK1 kinase insert domain receptor (a type III receptor tyrosine kinase) (VEGF receptor 2)| FLK1 kinase insert domain receptor (VEGF receptor 2)| flk-1 receptor| flk-1 type VEGF receptor| FLK/KDR| flk-type VEGF receptor| growth factor receptor tyrosine kinase| H920_12154| I79_022034| Kdrb| kinase insert domain protein receptor| kinase insert domain receptor (a type III receptor tyrosine kina| kinase insert domain receptor (a type III receptor tyrosine kinase)| kinase insert domain receptor (a type III receptor tyrosine kinase), b| kinase insert domain receptor-B| kinase NYK| Krd-1| Ly73| M959_12725| MDA_GLEAN10015832| N300_04129| N301_01918| N302_04106| N303_02715| N305_05155| N308_14550| N309_02342| N310_03021| N311_00564| N312_04278| N320_07716| N322_06964| N324_06629| N325_11573| N326_04235| N327_05636| N328_04786| N329_07089| N330_01811| N331_10569| N332_12332| N333_12200| N334_09382| N335_10036| N336_06612| N339_06932| N341_04725| PAL_GLEAN10016107| PANDA_008037| protein-tyrosine kinase receptor Flk-1| protein-tyrosine kinase receptor flk-1b| soluble vascular endothelial growth factor receptor 2| soluble VEGFR2| soluble VEGF receptor 2| sVEGFR-2| TREES_T100015831| tyrosine kinase growth factor receptor| tyrosine kinase receptor| tyrosine kinase receptor (flk-1)| UY3_17790| vascular endothelial growth factor receptor-2| Vascular endothelial growth factor receptor 2| vascular endothelial growth factor receptor 2 homolog B| vascular endothelial growth factor receptor-3| VEGFR| vegfr2| vegfr-2| vegfr2b| VEGFR-2 homolog B| VEGF receptor-2| VEGF receptor-2/Flk-1| xflk-1| Y1Q_030597| Y956_08129| Z169_11273| kdr

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