General Information of Binding Target of SBP (BTS) (ID: ST00033)
BTS Name
Vascular endothelial growth factor receptor 2
Synonyms
VEGFR-2; EC 2.7.10.1; Fetal liver kinase 1; FLK-1; Kinase insert domain receptor; KDR; Protein-tyrosine kinase receptor flk-1; CD antigen CD309
BTS Type
Protein
Family
Protein kinase superfamily;
Tyr protein kinase family;
CSF-1/PDGF receptor subfamily
Gene Name
KDR
Organism
Homo sapiens (Human)
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.
UniProt ID
P35968
UniProt Entry
VGFR2_HUMAN
PFam
PF07679 ; PF00047 ; PF07714 ; PF17988
Gene ID
3791
Sequence
MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLD
WLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQD
YRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWD
SKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGE
KLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRS
DQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPP
EIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVP
PQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPY
PCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGE
RVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPT
PVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLT
VLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNR
NLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWL
LLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPL
GRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVN
LLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLK
RRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLA
SRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDR
VYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTML
DCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVS
CMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDS
GMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYS
SEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV
Sequence Length
1356
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Affimer anti-VEGFR-2 A9 Research Inhibitor Kd: 41 nM Tools for modulators of protein function;tools for affinity histochemistry
SBP Info
[1]
Affimer anti-VEGFR-2 B8 Research Inhibitor Kd: 240 nM Tools for modulators of protein function;tools for affinity histochemistry
SBP Info
[1]
DARPin anti-VEGFR-2 D23b Research Inhibitor Kd: 0.01 nM Diagnostic reagent
SBP Info
[2], [3]
DARPin anti-VEGFR-2 D4b Research Inhibitor Kd: 0.19 nM Diagnostic reagent
SBP Info
[2], [3]
DARPin anti-VEGFR-2 D7b Research Inhibitor Kd: 0.37 nM Diagnostic reagent
SBP Info
[2], [3]
Fab Alacizumab Phase II Antagonist N.A. Non-small cell lung cancer [ICD-11: 2C25.Y]
SBP Info
[4]
Monobody anti-VEGFR-2 Research Binder Kd: 0.72 nM Research tool
SBP Info
[5]
Monobody anti-VEGFR-2 pAdHM72-alphaV-L2 Research Inhibitor Kd: 1.2 nM Targeted gene therapy
SBP Info
[6]
Monobody Pegdinetanib Phase II Inhibitor Kd: 11 nM Pancreatic cancer [ICD-11: 2C10.Z]; Non-Hodgkin lymphoma [ICD-11: 2B33.5]; Macular degeneration [ICD-11: 9B78.3Z]; Glioblastoma [ICD-11: XH7F82]; Colorectal cancer [ICD-11: 2B91.Z]; Non-small cell lung cancer [ICD-11: 2C25.Y]
SBP Info
[7], [8], [9]
Nanobody anti-VEGFR-2 NTV1 Research Inhibitor Kd: 49 nM Cancers [ICD-11: 2D4Z]
SBP Info
[10]
Nanobody anti-VEGFR-2 NTV2 Research Binder N.A. Cancers [ICD-11: 2D4Z]
SBP Info
[10]
Nanobody anti-VEGFR-2 NTV3 Research Binder N.A. Cancers [ICD-11: 2D4Z]
SBP Info
[10]
Nanobody anti-VEGFR-2 NTV4 Research Binder N.A. Cancers [ICD-11: 2D4Z]
SBP Info
[10]
WW domain anti-VEGFR-2 clone B1 Research Binder Kd: 44 nM Research tool
SBP Info
[11]
WW domain anti-VEGFR-2 cycB1_4-28 Research Binder Kd: 35 nM Research tool
SBP Info
[11]
WW domain anti-VEGFR-2 cycB1_6-36 Research Binder Kd: 67 nM Research tool
SBP Info
[11]
References
1 Affimer proteins are versatile and renewable affinity reagents. Elife. 2017 Jun 27;6:e24903.
2 Targeting extracellular domains D4 and D7 of vascular endothelial growth factor receptor 2 reveals allosteric receptor regulatory sites. Mol Cell Biol. 2012 Oct;32(19):3802-13.
3 High-affinity binders selected from designed ankyrin repeat protein libraries. Nat Biotechnol. 2004 May;22(5):575-82.
4 Emerging PEGylated drugs.Expert Opin Emerg Drugs. 2009 Jun;14(2):363-80.
5 Mutational and biophysical robustness in a prestabilized monobody. J Biol Chem. Jan-Jun 2021;296:100447.
6 A targeted adenovirus vector displaying a human fibronectin type III domain-based monobody in a fiber protein. Biomaterials. 2013 May;34(16):4191-4201.
7 In vitro-engineered non-antibody protein therapeutics. Protein Cell. 2018 Jan;9(1):3-14.
8 Recent advances in the development of novel protein scaffolds based therapeutics. Int J Biol Macromol. 2017 Sep;102:630-641.
9 KEGG DRUG Database. Pegdinetanib
10 Generation and characterization of a human nanobody against VEGFR-2. Acta Pharmacol Sin. 2016 Jun;37(6):857-64.
11 Selection of a high-affinity WW domain against the extracellular region of VEGF receptor isoform-2 from a combinatorial library using CIS display. Protein Eng Des Sel. 2013 Apr;26(4):307-15.