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Identification
HMDB Protein ID HMDBP01272
Secondary Accession Numbers
  • 6568
Name Vascular endothelial growth factor receptor 2
Synonyms
  1. CD309 antigen
  2. FLK-1
  3. Fetal liver kinase 1
  4. Kinase insert domain receptor
  5. Protein-tyrosine kinase receptor flk-1
  6. VEGFR-2
Gene Name KDR
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Receptor for VEGF or VEGFC. Has a tyrosine-protein kinase activity. The VEGF-kinase ligand/receptor signaling system plays a key role in vascular development and regulation of vascular permeability. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions
Pathways
  • Bevacizumab Action Pathway
  • Vatalanib Action Pathway
Reactions Not Available
GO Classification
Component
integral to plasma membrane
membrane
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
growth factor binding
nucleoside binding
vascular endothelial growth factor receptor activity
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein binding
protein kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
enzyme linked receptor protein signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
metabolic process
vascular endothelial growth factor receptor signaling pathway
cellular metabolic process
protein amino acid phosphorylation
signaling
signaling pathway
cell surface receptor linked signaling pathway
phosphorylation
Cellular Location
  1. Membrane
  2. Single-pass type I membrane protein
Gene Properties
Chromosome Location Chromosome:4
Locus 4q11-q12
SNPs KDR
Gene Sequence
>4071 bp
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
Protein Properties
Number of Residues 1356
Molecular Weight 151525.6
Theoretical pI 5.64
Pfam Domain Function
Signals
  • 1-19
Transmembrane Regions
  • 765-789
Protein Sequence
>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
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P35968
UniProtKB/Swiss-Prot Entry Name VGFR2_HUMAN
PDB IDs Not Available
GenBank Gene ID AF035121
GeneCard ID KDR
GenAtlas ID KDR
HGNC ID HGNC:6307
References
General References
  1. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  2. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
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  4. Walter JW, North PE, Waner M, Mizeracki A, Blei F, Walker JW, Reinisch JF, Marchuk DA: Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma. Genes Chromosomes Cancer. 2002 Mar;33(3):295-303. [PubMed:11807987 ]
  5. Terman BI, Carrion ME, Kovacs E, Rasmussen BA, Eddy RL, Shows TB: Identification of a new endothelial cell growth factor receptor tyrosine kinase. Oncogene. 1991 Sep;6(9):1677-83. [PubMed:1656371 ]
  6. Patterson C, Perrella MA, Hsieh CM, Yoshizumi M, Lee ME, Haber E: Cloning and functional analysis of the promoter for KDR/flk-1, a receptor for vascular endothelial growth factor. J Biol Chem. 1995 Sep 29;270(39):23111-8. [PubMed:7559454 ]
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  10. Mellberg S, Dimberg A, Bahram F, Hayashi M, Rennel E, Ameur A, Westholm JO, Larsson E, Lindahl P, Cross MJ, Claesson-Welsh L: Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis. FASEB J. 2009 May;23(5):1490-502. doi: 10.1096/fj.08-123810. Epub 2009 Jan 9. [PubMed:19136612 ]
  11. McTigue MA, Wickersham JA, Pinko C, Showalter RE, Parast CV, Tempczyk-Russell A, Gehring MR, Mroczkowski B, Kan CC, Villafranca JE, Appelt K: Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis. Structure. 1999 Mar 15;7(3):319-30. [PubMed:10368301 ]
  12. Miyazaki Y, Matsunaga S, Tang J, Maeda Y, Nakano M, Philippe RJ, Shibahara M, Liu W, Sato H, Wang L, Nolte RT: Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors. Bioorg Med Chem Lett. 2005 May 2;15(9):2203-7. [PubMed:15837294 ]
  13. Hodous BL, Geuns-Meyer SD, Hughes PE, Albrecht BK, Bellon S, Bready J, Caenepeel S, Cee VJ, Chaffee SC, Coxon A, Emery M, Fretland J, Gallant P, Gu Y, Hoffman D, Johnson RE, Kendall R, Kim JL, Long AM, Morrison M, Olivieri PR, Patel VF, Polverino A, Rose P, Tempest P, Wang L, Whittington DA, Zhao H: Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor. J Med Chem. 2007 Feb 22;50(4):611-26. Epub 2007 Jan 25. [PubMed:17253678 ]
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