Homo sapiens KDR
Vascular endothelial growth factor receptor 2 | Protein names
Vascular endothelial growth factor receptor 2 | Alternative names
Fetal liver kinase 1, Kinase insert domain receptor, Protein-tyrosine kinase receptor flk-1 | Gene names
KDR | Protein family
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily | 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
L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)
| Subcellular location
Secreted | Structure
(Microbial infection) Interacts with HIV-1 Tat | Post-translational modification
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
| Involvement in disease
Hemangioma, capillary infantile
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.
| Keywords
3D-structure, Alternative splicing, Angiogenesis, ATP-binding, Cell junction, Cell membrane, Cytoplasm, Cytoplasmic vesicle, Developmental protein, Differentiation, Disulfide bond, Endoplasmic reticulum, Endosome, Glycoprotein, Host-virus interaction, Immunoglobulin domain, Kinase, Membrane, Nucleotide-binding, Nucleus, Phosphoprotein, Proteomics identification, Receptor, Reference proteome, Repeat, Secreted, Signal, Transferase, Transmembrane, Transmembrane helix, Tyrosine-protein kinase, Ubl conjugation | Sequence
MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLD WLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQD YRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWD SKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGE KLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRS DQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPP EIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVP PQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPY PCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGE RVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPT PVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLT VLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNR NLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWL LLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPL GRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVN LLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLK RRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLA SRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDR VYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTML DCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVS CMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDS GMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYS SEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV | | UniProt accession: P35968 |
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