Vascular endothelial growth factor receptor 2
Also known as: FLK1, KDR, VEGFR2
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.
Classification
- Family (Pfam)
- PF07679 I-set, PF00047 ig, PF13895 Ig_2, PF22971 Ig_VEGFR-1-like_5th, PF07714 PK_Tyr_Ser-Thr, PF21339 VEGFR-1-like_Ig-like, PF17988 VEGFR-2_TMD, PF22854 VEGFR1-3_N_Ig-like
- InterPro
- Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_I-set, Ig_sub, Ig_sub2, Immunoglobulin_dom, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS, VEGFR-2_TMD, VEGFR1-3_5th, VEGFR1-3_N_Ig-like, VEGFR2_rcpt
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 54
- 1VR2 X-ray 2.40A
- 1Y6A X-ray 2.10A
- 1Y6B X-ray 2.10A
- 1YWN X-ray 1.71A
- 2M59 NMR
- 2MET NMR
- 2MEU NMR
- 2OH4 X-ray 2.05A
- 2P2H X-ray 1.95A
- 2P2I X-ray 2.40A
- 2QU5 X-ray 2.95A
- 2QU6 X-ray 2.10A
- … and 42 more
A predicted model is available from AlphaFold.
Gene Ontology · 68
- GO:0070161 anchoring junction
- GO:0030054 cell junction
- GO:0005829 cytosol
- GO:0005769 early endosome
- GO:0005783 endoplasmic reticulum
- GO:0005768 endosome
- GO:0009897 external side of plasma membrane
- GO:0005576 extracellular region
- GO:0005794 Golgi apparatus
- GO:0045121 membrane raft
- GO:0031965 nuclear membrane
- GO:0005886 plasma membrane
- GO:0043235 receptor complex
- GO:0097443 sorting endosome
- GO:0005524 ATP binding
- GO:0045296 cadherin binding
- GO:0015026 coreceptor activity
- GO:0019838 growth factor binding
- GO:0051879 Hsp90 protein binding
- GO:0042802 identical protein binding
- GO:0005178 integrin binding
- GO:0004713 protein tyrosine kinase activity
- GO:0004714 transmembrane receptor protein tyrosine kinase activity
- GO:0038085 vascular endothelial growth factor binding
- GO:0005021 vascular endothelial growth factor receptor activity
- GO:0001525 angiogenesis
- GO:0001569 branching involved in blood vessel morphogenesis
- GO:0016477 cell migration
- GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
- GO:1904881 cellular response to hydrogen sulfide
- GO:0035924 cellular response to vascular endothelial growth factor stimulus
- GO:0035162 embryonic hemopoiesis
- GO:0003157 endocardium development
- GO:0045446 endothelial cell differentiation
- GO:0003158 endothelium development
- GO:2000352 negative regulation of endothelial cell apoptotic process
- GO:0010629 negative regulation of gene expression
- GO:0043524 negative regulation of neuron apoptotic process
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0045766 positive regulation of angiogenesis
- GO:0043536 positive regulation of blood vessel endothelial cell migration
- GO:0030513 positive regulation of BMP signaling pathway
- GO:0030335 positive regulation of cell migration
- GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis
- GO:0008284 positive regulation of cell population proliferation
- GO:2001028 positive regulation of endothelial cell chemotaxis
- GO:0010595 positive regulation of endothelial cell migration
- GO:0001938 positive regulation of endothelial cell proliferation
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0051894 positive regulation of focal adhesion assembly
- GO:0016239 positive regulation of macroautophagy
- GO:0043410 positive regulation of MAPK cascade
- GO:0051901 positive regulation of mitochondrial depolarization
- GO:0090141 positive regulation of mitochondrial fission
- GO:0141150 positive regulation of nitric oxide-cGMP mediated signal transduction
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0050927 positive regulation of positive chemotaxis
- GO:0001934 positive regulation of protein phosphorylation
- GO:2001214 positive regulation of vasculogenesis
- GO:0046777 protein autophosphorylation
- GO:0008360 regulation of cell shape
- GO:0043408 regulation of MAPK cascade
- GO:0071526 semaphorin-plexin signaling pathway
- GO:0048010 vascular endothelial growth factor receptor signaling pathway
- GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway
- GO:0038084 vascular endothelial growth factor signaling pathway
- GO:0061042 vascular wound healing
- GO:0001570 vasculogenesis
Disease associations
- capillary infantile hemangioma MONDO:0011191
Drugs targeting this protein · 64
- VATALANIB inhibitor
- SORAFENIB TOSYLATE inhibitor
- PAZOPANIB HYDROCHLORIDE inhibitor
- FORETINIB inhibitor
- HENATINIB inhibitor
- FAMITINIB inhibitor
- TIVOZANIB inhibitor
- AXITINIB inhibitor
- CEP-5214 inhibitor
- SUNITINIB MALATE inhibitor
- OSI-930 inhibitor
- SU-014813 inhibitor
- PF-00337210 inhibitor
- REGORAFENIB inhibitor
- ILORASERTIB inhibitor
- RG-1530 inhibitor
- CEP-11981 inhibitor
- TELATINIB inhibitor
- CABOZANTINIB S-MALATE inhibitor
- LENVATINIB MESYLATE inhibitor
- TIVOZANIB HYDROCHLORIDE inhibitor
- BMS-794833 inhibitor
- TAK-593 inhibitor
- LUCITANIB inhibitor
- LINIFANIB inhibitor
- VANDETANIB inhibitor
- OSI-632 inhibitor
- BRIVANIB ALANINATE inhibitor
- ORANTINIB inhibitor
- SEMAXANIB inhibitor
- NINTEDANIB ESYLATE inhibitor
- GOLVATINIB inhibitor
- L-21649 inhibitor
- CEP-7055 inhibitor
- ZD-4190 inhibitor
- JI-101 inhibitor
- AG-13958 inhibitor
- ALTIRATINIB inhibitor
- BMS-690514 inhibitor
- RIVOCERANIB MESYLATE inhibitor
- TAS-115 inhibitor
- BRIVANIB inhibitor
- NINGETINIB inhibitor
- GLESATINIB inhibitor
- TG100-801 inhibitor
- KRN-633 inhibitor
- BFH-772 inhibitor
- SURUFATINIB inhibitor
- CATEQUENTINIB inhibitor
- FRUQUINTINIB inhibitor
- PUQUITINIB MESYLATE DIHYDRATE inhibitor
- CYC-116 inhibitor
- ENMD-2076 inhibitor
- CEDIRANIB inhibitor
- IBCASERTIB inhibitor
- DOVITINIB inhibitor
- ENMD-981693 inhibitor
- XL-999 inhibitor
- 4SC-203 inhibitor
- SUNITINIB inhibitor
- RAF-265 inhibitor
- MOTESANIB inhibitor
- AEE-788 inhibitor
- MIDOSTAURIN inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Vascular endothelial growth factor receptor 2 0.98
- Vascular endothelial growth factor receptor 2 0.98
- Vascular endothelial growth factor receptor 2 0.97
- Vascular endothelial growth factor receptor 3 0.94
- Vascular endothelial growth factor receptor 2 0.94
- Vascular endothelial growth factor receptor 3 0.93
- Vascular endothelial growth factor receptor kdr-like 0.92
- Vascular endothelial growth factor receptor 1 0.90
- Vascular endothelial growth factor receptor 1 0.90
- Vascular endothelial growth factor receptor 1 0.89
- Vascular endothelial growth factor receptor 1 0.89
- Vascular endothelial growth factor receptor 3 0.87
Co-cited proteins · studied together in the literature
- Vascular endothelial growth factor receptor 2 5 shared papers
- SH2 domain-containing protein 2A 1 shared papers
- Vascular endothelial growth factor receptor 1 6 shared papers
- Vascular endothelial growth factor receptor 3 7 shared papers
- Phosducin-like protein 3 2 shared papers
- Anthrax toxin receptor 1 1 shared papers
- Vascular endothelial growth factor C 1 shared papers
- Receptor-type tyrosine-protein phosphatase beta 1 shared papers
- 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 2 shared papers
- Programmed cell death protein 6 1 shared papers
- Phosducin-like protein 3 1 shared papers
- Angiopoietin-1 receptor 1 shared papers
Literature · 61 cited papers
- Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis. Nat. Cell Biol. · 2022
- Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis. Angiogenesis · 2015
- EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its activation by VEGF. Oncotarget · 2015
- Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin. Mol. Biol. Cell · 2014
- Identification of PDCL3 as a novel chaperone protein involved in the generation of functional VEGF receptor 2. J. Biol. Chem. · 2013
- Vascular endothelial cell growth-activated XBP1 splicing in endothelial cells is crucial for angiogenesis. Circulation · 2013
- VEGFR2 functions as an H(2)S-targeting receptor protein kinase with its novel Cys1045-Cys1024 disulfide bond serving as a specific molecular switch for hydrogen sulfide actions in vascular endothelial cells. Antioxid. Redox Signal. · 2013
- Programmed cell death 6 (PDCD6) inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2. Cell. Signal. · 2012
- The structural basis for the function of two anti-VEGF receptor 2 antibodies. Structure · 2011
- Tyrosine kinase receptor Flt/VEGFR family: its characterization related to angiogenesis and cancer. Genes Cancer · 2010
- Signal transduction by vascular endothelial growth factor receptors. Biochem. J. · 2011
- The VEGFR2 receptor tyrosine kinase undergoes constitutive endosome-to-plasma membrane recycling. Biochem. Biophys. Res. Commun. · 2011
- … and 49 more in the literature graph