Vascular endothelial growth factor receptor 2

Details

Name
Vascular endothelial growth factor receptor 2
Synonyms
  • 2.7.10.1
  • Fetal liver kinase 1
  • FLK-1
  • FLK1
  • KDR
  • Kinase insert domain receptor
  • Protein-tyrosine kinase receptor flk-1
  • VEGFR-2
  • VEGFR2
Gene Name
KDR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000735|Vascular endothelial growth factor receptor 2
MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLD
WLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQD
YRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWD
SKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGE
KLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRS
DQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPP
EIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVP
PQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPY
PCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGE
RVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPT
PVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLT
VLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNR
NLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWL
LLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPL
GRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVN
LLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLK
RRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLA
SRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDR
VYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTML
DCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVS
CMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDS
GMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYS
SEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV
Number of residues
1356
Molecular Weight
151525.555
Theoretical pI
5.64
GO Classification
Functions
ATP binding / growth factor binding / Hsp90 protein binding / integrin binding / protein tyrosine kinase activity / receptor signaling protein tyrosine kinase activity / transmembrane receptor protein tyrosine kinase activity / vascular endothelial growth factor binding / vascular endothelial growth factor-activated receptor activity
Processes
angiogenesis / branching morphogenesis of an epithelial tube / calcium ion homeostasis / calcium-mediated signaling using intracellular calcium source / cell fate commitment / cell maturation / cell migration involved in sprouting angiogenesis / cellular response to vascular endothelial growth factor stimulus / embryonic hemopoiesis / endothelial cell differentiation / endothelium development / extracellular matrix organization / lung alveolus development / lymph vessel development / negative regulation of apoptotic process / negative regulation of endothelial cell apoptotic process / ovarian follicle development / 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 migration / positive regulation of endothelial cell proliferation / positive regulation of ERK1 and ERK2 cascade / positive regulation of focal adhesion assembly / positive regulation of MAPK cascade / positive regulation of mesenchymal cell proliferation / 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 / regulation of endothelial cell differentiation / regulation of hematopoietic progenitor cell differentiation / signal transduction by protein phosphorylation / surfactant homeostasis / transmembrane receptor protein tyrosine kinase signaling pathway / vascular endothelial growth factor receptor signaling pathway / vascular endothelial growth factor signaling pathway / vasculogenesis / viral process
Components
cell junction / cytoplasmic membrane-bounded vesicle / early endosome / endoplasmic reticulum / endosome / external side of plasma membrane / extracellular region / Golgi apparatus / integral component of plasma membrane / membrane raft / nucleus / plasma membrane / sorting endosome
General Function
Vascular endothelial growth factor-activated receptor activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
765-785
Cellular Location
Cell junction
Gene sequence
>lcl|BSEQ0020462|Vascular endothelial growth factor receptor 2 (KDR)
ATGCAGAGCAAGGTGCTGCTGGCCGTCGCCCTGTGGCTCTGCGTGGAGACCCGGGCCGCC
TCTGTGGGTTTGCCTAGTGTTTCTCTTGATCTGCCCAGGCTCAGCATACAAAAAGACATA
CTTACAATTAAGGCTAATACAACTCTTCAAATTACTTGCAGGGGACAGAGGGACTTGGAC
TGGCTTTGGCCCAATAATCAGAGTGGCAGTGAGCAAAGGGTGGAGGTGACTGAGTGCAGC
GATGGCCTCTTCTGTAAGACACTCACAATTCCAAAAGTGATCGGAAATGACACTGGAGCC
TACAAGTGCTTCTACCGGGAAACTGACTTGGCCTCGGTCATTTATGTCTATGTTCAAGAT
TACAGATCTCCATTTATTGCTTCTGTTAGTGACCAACATGGAGTCGTGTACATTACTGAG
AACAAAAACAAAACTGTGGTGATTCCATGTCTCGGGTCCATTTCAAATCTCAACGTGTCA
CTTTGTGCAAGATACCCAGAAAAGAGATTTGTTCCTGATGGTAACAGAATTTCCTGGGAC
AGCAAGAAGGGCTTTACTATTCCCAGCTACATGATCAGCTATGCTGGCATGGTCTTCTGT
GAAGCAAAAATTAATGATGAAAGTTACCAGTCTATTATGTACATAGTTGTCGTTGTAGGG
TATAGGATTTATGATGTGGTTCTGAGTCCGTCTCATGGAATTGAACTATCTGTTGGAGAA
AAGCTTGTCTTAAATTGTACAGCAAGAACTGAACTAAATGTGGGGATTGACTTCAACTGG
GAATACCCTTCTTCGAAGCATCAGCATAAGAAACTTGTAAACCGAGACCTAAAAACCCAG
TCTGGGAGTGAGATGAAGAAATTTTTGAGCACCTTAACTATAGATGGTGTAACCCGGAGT
GACCAAGGATTGTACACCTGTGCAGCATCCAGTGGGCTGATGACCAAGAAGAACAGCACA
TTTGTCAGGGTCCATGAAAAACCTTTTGTTGCTTTTGGAAGTGGCATGGAATCTCTGGTG
GAAGCCACGGTGGGGGAGCGTGTCAGAATCCCTGCGAAGTACCTTGGTTACCCACCCCCA
GAAATAAAATGGTATAAAAATGGAATACCCCTTGAGTCCAATCACACAATTAAAGCGGGG
CATGTACTGACGATTATGGAAGTGAGTGAAAGAGACACAGGAAATTACACTGTCATCCTT
ACCAATCCCATTTCAAAGGAGAAGCAGAGCCATGTGGTCTCTCTGGTTGTGTATGTCCCA
CCCCAGATTGGTGAGAAATCTCTAATCTCTCCTGTGGATTCCTACCAGTACGGCACCACT
CAAACGCTGACATGTACGGTCTATGCCATTCCTCCCCCGCATCACATCCACTGGTATTGG
CAGTTGGAGGAAGAGTGCGCCAACGAGCCCAGCCAAGCTGTCTCAGTGACAAACCCATAC
CCTTGTGAAGAATGGAGAAGTGTGGAGGACTTCCAGGGAGGAAATAAAATTGAAGTTAAT
AAAAATCAATTTGCTCTAATTGAAGGAAAAAACAAAACTGTAAGTACCCTTGTTATCCAA
GCGGCAAATGTGTCAGCTTTGTACAAATGTGAAGCGGTCAACAAAGTCGGGAGAGGAGAG
AGGGTGATCTCCTTCCACGTGACCAGGGGTCCTGAAATTACTTTGCAACCTGACATGCAG
CCCACTGAGCAGGAGAGCGTGTCTTTGTGGTGCACTGCAGACAGATCTACGTTTGAGAAC
CTCACATGGTACAAGCTTGGCCCACAGCCTCTGCCAATCCATGTGGGAGAGTTGCCCACA
CCTGTTTGCAAGAACTTGGATACTCTTTGGAAATTGAATGCCACCATGTTCTCTAATAGC
ACAAATGACATTTTGATCATGGAGCTTAAGAATGCATCCTTGCAGGACCAAGGAGACTAT
GTCTGCCTTGCTCAAGACAGGAAGACCAAGAAAAGACATTGCGTGGTCAGGCAGCTCACA
GTCCTAGAGCGTGTGGCACCCACGATCACAGGAAACCTGGAGAATCAGACGACAAGTATT
GGGGAAAGCATCGAAGTCTCATGCACGGCATCTGGGAATCCCCCTCCACAGATCATGTGG
TTTAAAGATAATGAGACCCTTGTAGAAGACTCAGGCATTGTATTGAAGGATGGGAACCGG
AACCTCACTATCCGCAGAGTGAGGAAGGAGGACGAAGGCCTCTACACCTGCCAGGCATGC
AGTGTTCTTGGCTGTGCAAAAGTGGAGGCATTTTTCATAATAGAAGGTGCCCAGGAAAAG
ACGAACTTGGAAATCATTATTCTAGTAGGCACGGCGGTGATTGCCATGTTCTTCTGGCTA
CTTCTTGTCATCATCCTACGGACCGTTAAGCGGGCCAATGGAGGGGAACTGAAGACAGGC
TACTTGTCCATCGTCATGGATCCAGATGAACTCCCATTGGATGAACATTGTGAACGACTG
CCTTATGATGCCAGCAAATGGGAATTCCCCAGAGACCGGCTGAAGCTAGGTAAGCCTCTT
GGCCGTGGTGCCTTTGGCCAAGTGATTGAAGCAGATGCCTTTGGAATTGACAAGACAGCA
ACTTGCAGGACAGTAGCAGTCAAAATGTTGAAAGAAGGAGCAACACACAGTGAGCATCGA
GCTCTCATGTCTGAACTCAAGATCCTCATTCATATTGGTCACCATCTCAATGTGGTCAAC
CTTCTAGGTGCCTGTACCAAGCCAGGAGGGCCACTCATGGTGATTGTGGAATTCTGCAAA
TTTGGAAACCTGTCCACTTACCTGAGGAGCAAGAGAAATGAATTTGTCCCCTACAAGACC
AAAGGGGCACGATTCCGTCAAGGGAAAGACTACGTTGGAGCAATCCCTGTGGATCTGAAA
CGGCGCTTGGACAGCATCACCAGTAGCCAGAGCTCAGCCAGCTCTGGATTTGTGGAGGAG
AAGTCCCTCAGTGATGTAGAAGAAGAGGAAGCTCCTGAAGATCTGTATAAGGACTTCCTG
ACCTTGGAGCATCTCATCTGTTACAGCTTCCAAGTGGCTAAGGGCATGGAGTTCTTGGCA
TCGCGAAAGTGTATCCACAGGGACCTGGCGGCACGAAATATCCTCTTATCGGAGAAGAAC
GTGGTTAAAATCTGTGACTTTGGCTTGGCCCGGGATATTTATAAAGATCCAGATTATGTC
AGAAAAGGAGATGCTCGCCTCCCTTTGAAATGGATGGCCCCAGAAACAATTTTTGACAGA
GTGTACACAATCCAGAGTGACGTCTGGTCTTTTGGTGTTTTGCTGTGGGAAATATTTTCC
TTAGGTGCTTCTCCATATCCTGGGGTAAAGATTGATGAAGAATTTTGTAGGCGATTGAAA
GAAGGAACTAGAATGAGGGCCCCTGATTATACTACACCAGAAATGTACCAGACCATGCTG
GACTGCTGGCACGGGGAGCCCAGTCAGAGACCCACGTTTTCAGAGTTGGTGGAACATTTG
GGAAATCTCTTGCAAGCTAATGCTCAGCAGGATGGCAAAGACTACATTGTTCTTCCGATA
TCAGAGACTTTGAGCATGGAAGAGGATTCTGGACTCTCTCTGCCTACCTCACCTGTTTCC
TGTATGGAGGAGGAGGAAGTATGTGACCCCAAATTCCATTATGACAACACAGCAGGAATC
AGTCAGTATCTGCAGAACAGTAAGCGAAAGAGCCGGCCTGTGAGTGTAAAAACATTTGAA
GATATCCCGTTAGAAGAACCAGAAGTAAAAGTAATCCCAGATGACAACCAGACGGACAGT
GGTATGGTTCTTGCCTCAGAAGAGCTGAAAACTTTGGAAGACAGAACCAAATTATCTCCA
TCTTTTGGTGGAATGGTGCCCAGCAAAAGCAGGGAGTCTGTGGCATCTGAAGGCTCAAAC
CAGACAAGCGGCTACCAGTCCGGATATCACTCCGATGACACAGACACCACCGTGTACTCC
AGTGAGGAAGCAGAACTTTTAAAGCTGATAGAGATTGGAGTGCAAACCGGTAGCACAGCC
CAGATTCTCCAGCCTGACTCGGGGACCACACTGAGCTCTCCTCCTGTTTAA
Chromosome Location
4
Locus
4q11-q12
External Identifiers
ResourceLink
UniProtKB IDP35968
UniProtKB Entry NameVGFR2_HUMAN
GenBank Protein ID2655412
GenBank Gene IDAF035121
GenAtlas IDKDR
HGNC IDHGNC:6307
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00398Sorafenibapproved, investigationalyesantagonistDetails
DB01268Sunitinibapproved, investigationalyesinhibitorDetails
DB04849CediranibinvestigationalunknownDetails
DB04879VatalanibinvestigationalunknownDetails
DB12307ForetinibinvestigationalunknownDetails
DB05198CYC116investigationalunknownDetails
DB05014XL999investigationalunknownDetails
DB05075TG-100801investigationalunknownDetails
DB04727N-(4-{4-AMINO-6-[4-(METHYLOXY)PHENYL]FURO[2,3-D]PYRIMIDIN-5-YL}PHENYL)-N'-[2-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]UREAexperimentalunknownDetails
DB05146XL820investigationalunknownDetails
DB06080ABT-869investigationalunknownDetails
DB06101IMC-1C11investigationalunknownDetails
DB05931PegdinetanibinvestigationalunknownDetails
DB05984RAF-265investigationalunknownDetails
DB06436SemaxanibinvestigationalunknownDetails
DB06589PazopanibapprovedyesinhibitorDetails
DB06595Midostaurinapproved, investigationalyesantagonistinhibitorDetails
DB06626Axitinibapproved, investigationalyesinhibitorDetails
DB069384-[[2-[[4-chloro-3-(trifluoromethyl)phenyl]amino]-3H-benzimidazol-5-yl]oxy]-N-methyl-pyridine-2-carboxamideexperimentalunknownDetails
DB07183N-(4-phenoxyphenyl)-2-[(pyridin-4-ylmethyl)amino]nicotinamideexperimentalunknownDetails
DB07274N-cyclopropyl-6-[(6,7-dimethoxyquinolin-4-yl)oxy]naphthalene-1-carboxamideexperimentalunknownDetails
DB073266-chloro-N-pyrimidin-5-yl-3-{[3-(trifluoromethyl)phenyl]amino}-1,2-benzisoxazole-7-carboxamideexperimentalunknownDetails
DB07333N-(CYCLOPROPYLMETHYL)-4-(METHYLOXY)-3-({5-[3-(3-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-YL}AMINO)BENZENESULFONAMIDEexperimentalunknownDetails
DB07334N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINEexperimentalunknownDetails
DB075143-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-oneexperimentalunknownDetails
DB075283-(2-aminoquinazolin-6-yl)-4-methyl-1-[3-(trifluoromethyl)phenyl]pyridin-2(1H)-oneexperimentalunknownDetails
DB07537N'-(6-aminopyridin-3-yl)-N-(2-cyclopentylethyl)-4-methyl-benzene-1,3-dicarboxamideexperimentalunknownDetails
DB08042N~4~-methyl-N~4~-(3-methyl-1H-indazol-6-yl)-N~2~-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamineexperimentalunknownDetails
DB08519N~4~-(3-methyl-1H-indazol-6-yl)-N~2~-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamineexperimentalunknownDetails
DB08875Cabozantinibapproved, investigationalyesantagonistDetails
DB08896RegorafenibapprovedyesinhibitorDetails
DB08901Ponatinibapproved, investigationalunknowninhibitorDetails
DB09078Lenvatinibapproved, investigationalyesinhibitorDetails
DB09079NintedanibapprovedyesinhibitorDetails
DB05578Ramucirumabapproved, investigationalyesantagonistDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB12147Erdafitinibapproved, investigationalunknownsubstrateDetails