KDR
entrez
3791
canonical
uniprot
P35968
canonical
ensembl
ENSG00000128052
resolver
ensp
ENSP00000263923
resolver
genesymbol
KDR
resolver
genesymbol_syn
FLK1
resolver
genesymbol_syn
VEGFR2
resolver
hgnc
HGNC:6307
resolver
uniprot
A2RRS0
resolver
uniprot
B5A925
resolver
uniprot
C5IFA0
resolver
uniprot
O60723
resolver
uniprot
Q14178
resolver
uniprot_entry
VGFR2_HUMAN
resolver
uniprot_sec
A2RRS0
resolver
uniprot_sec
B5A925
resolver
uniprot_sec
C5IFA0
resolver
uniprot_sec
O60723
resolver
uniprot_sec
Q14178
resolver
activity_regulation
ACTIVITY 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. {ECO:0000269|PubMed:10037737, ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:23199280}.
uniprot
proteins
amino_acid_sequence
MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLDWLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQDYRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWDSKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPPEIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVPPQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPYPCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGERVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPTPVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLTVLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNRNLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWLLLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLKRRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVSCMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDSGMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYSSEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV
uniprot
proteins
disease_involvement
DISEASE: Hemangioma, capillary infantile (HCI) [MIM:602089]: 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. {ECO:0000269|PubMed:11807987, ECO:0000269|PubMed:18931684}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Note=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.
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
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. {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, ECO:0000269|PubMed:10600473, ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:1417831, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17303569, ECO:0000269|PubMed:18529047, ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:19834490, ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:7929439, ECO:0000269|PubMed:9160888, ECO:0000269|PubMed:9804796, ECO:0000269|PubMed:9837777}.
uniprot
proteins
mass_dalton
151527
uniprot
proteins
mutagenesis
MUTAGEN 726; /note="R->A: Strongly reduced autophosphorylation and activation of MAP kinases."; /evidence="ECO:0000269|PubMed:20080685"; MUTAGEN 731; /note="D->A: Strongly reduced autophosphorylation and activation of MAP kinases."; /evidence="ECO:0000269|PubMed:20080685"; MUTAGEN 801; /note="Y->F: Abolishes stimulation of nitric oxide synthesis."; /evidence="ECO:0000269|PubMed:17303569"; MUTAGEN 868; /note="K->M: Loss of enzyme activity."; /evidence="ECO:0000269|PubMed:11387210"; MUTAGEN 951; /note="Y->F: Abolishes reorganization of the actin cytoskeleton and cell migration in response to VEGFA."; /evidence="ECO:0000269|PubMed:15962004"; MUTAGEN 996; /note="Y->F: Strongly reduced autophosphorylation. Reduces phosphorylation of PLCG1."; /evidence="ECO:0000269|PubMed:10102632"; MUTAGEN 1045; /note="C->A: Significantly higher kinase activity."; /evidence="ECO:0000269|PubMed:23199280"; MUTAGEN 1054; /note="Y->F: Strongly reduced autophosphorylation. Abolishes phosphorylation of downstream signaling proteins; when associated with F-1059."; /evidence="ECO:0000269|PubMed:10102632"; MUTAGEN 1059; /note="Y->F: Strongly reduced autophosphorylation. Abolishes phosphorylation of downstream signaling proteins; when associated with F-1054."; /evidence="ECO:0000269|PubMed:10102632"; MUTAGEN 1175; /note="Y->F: Abolishes phosphorylation of PLCG1 and MAP kinases in response to VEGFA."; /evidence="ECO:0000269|PubMed:11387210"; MUTAGEN 1214; /note="Y->F: Loss of phosphorylation site. Abolishes reorganization of the actin cytoskeleton in response to VEGFA."; /evidence="ECO:0000269|PubMed:16966330
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:20145116, ECO:0000269|PubMed:21827946, ECO:0000269|PubMed:9160888}.; PTM: Ubiquitinated. Tyrosine phosphorylation of the receptor promotes its poly-ubiquitination, leading to its degradation via the proteasome or lysosomal proteases. {ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:17004325, ECO:0000269|PubMed:19834490}.; 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-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. {ECO:0000269|PubMed:10037737, ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:18936167, ECO:0000269|PubMed:19136612, ECO:0000269|PubMed:25825981}.; PTM: 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.
uniprot
proteins
protein_family
CSF-1/PDGF receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10037737
uniprot
proteins
pubmed
10102632
uniprot
proteins
pubmed
10368301
uniprot
proteins
pubmed
10590123
uniprot
proteins
pubmed
10600473
uniprot
proteins
pubmed
11387210
uniprot
proteins
pubmed
11807987
uniprot
proteins
pubmed
12649282
uniprot
proteins
pubmed
12881528
uniprot
proteins
pubmed
1417831
uniprot
proteins
pubmed
14991896
uniprot
proteins
pubmed
15026417
uniprot
proteins
pubmed
15215251
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
15837294
uniprot
proteins
pubmed
15962004
uniprot
proteins
pubmed
1656371
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
16966330
uniprot
proteins
pubmed
17002866
uniprot
proteins
pubmed
17004325
uniprot
proteins
pubmed
17253678
uniprot
proteins
pubmed
17303569
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17658244
uniprot
proteins
pubmed
18529047
uniprot
proteins
pubmed
18593464
uniprot
proteins
pubmed
18680722
uniprot
proteins
pubmed
18931684
uniprot
proteins
pubmed
18936167
uniprot
proteins
pubmed
19033661
uniprot
proteins
pubmed
19136612
uniprot
proteins
pubmed
19230644
uniprot
proteins
pubmed
19668192
uniprot
proteins
pubmed
19761875
uniprot
proteins
pubmed
19834490
uniprot
proteins
pubmed
20080685
uniprot
proteins
pubmed
20145116
uniprot
proteins
pubmed
20179233
uniprot
proteins
pubmed
20224550
uniprot
proteins
pubmed
20462514
uniprot
proteins
pubmed
20705758
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21539813
uniprot
proteins
pubmed
21711246
uniprot
proteins
pubmed
21779435
uniprot
proteins
pubmed
21827946
uniprot
proteins
pubmed
21893193
uniprot
proteins
pubmed
23199280
uniprot
proteins
pubmed
23529610
uniprot
proteins
pubmed
23792958
uniprot
proteins
pubmed
25187647
uniprot
proteins
pubmed
25825981
uniprot
proteins
pubmed
26059764
uniprot
proteins
pubmed
35027734
uniprot
proteins
pubmed
7559454
uniprot
proteins
pubmed
7929439
uniprot
proteins
pubmed
9160888
uniprot
proteins
pubmed
9804796
uniprot
proteins
pubmed
9837777
uniprot
proteins
sequence_length
1356
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell junction {ECO:0000250}. Endoplasmic reticulum {ECO:0000269|PubMed:23529610}. Cell membrane {ECO:0000269|PubMed:25825981}. Note=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). {ECO:0000250, ECO:0000269|PubMed:23529610}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I membrane protein. Cytoplasm. Nucleus. Cytoplasmic vesicle. Early endosome. 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.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.; SUBCELLULAR LOCATION: [Isoform 3]: Secreted.
uniprot
proteins
transmembrane_region
TRANSMEM 765..785; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins