General Information of Target

Target ID LDTP02932
Target Name Vascular endothelial growth factor receptor 1 (FLT1)
Gene Name FLT1
Gene ID 2321
Synonyms
FLT; FRT; VEGFR1; Vascular endothelial growth factor receptor 1; VEGFR-1; EC 2.7.10.1; Fms-like tyrosine kinase 1; FLT-1; Tyrosine-protein kinase FRT; Tyrosine-protein kinase receptor FLT; FLT; Vascular permeability factor receptor
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MVSYWDTGVLLCALLSCLLLTGSSSGSKLKDPELSLKGTQHIMQAGQTLHLQCRGEAAHK
WSLPEMVSKESERLSITKSACGRNGKQFCSTLTLNTAQANHTGFYSCKYLAVPTSKKKET
ESAIYIFISDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPD
GKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVQISTPRPV
KLLRGHTLVLNCTATTPLNTRVQMTWSYPDEKNKRASVRRRIDQSNSHANIFYSVLTIDK
MQNKDKGLYTCRVRSGPSFKSVNTSVHIYDKAFITVKHRKQQVLETVAGKRSYRLSMKVK
AFPSPEVVWLKDGLPATEKSARYLTRGYSLIIKDVTEEDAGNYTILLSIKQSNVFKNLTA
TLIVNVKPQIYEKAVSSFPDPALYPLGSRQILTCTAYGIPQPTIKWFWHPCNHNHSEARC
DFCSNNEESFILDADSNMGNRIESITQRMAIIEGKNKMASTLVVADSRISGIYICIASNK
VGTVGRNISFYITDVPNGFHVNLEKMPTEGEDLKLSCTVNKFLYRDVTWILLRTVNNRTM
HYSISKQKMAITKEHSITLNLTIMNVSLQDSGTYACRARNVYTGEEILQKKEITIRDQEA
PYLLRNLSDHTVAISSSTTLDCHANGVPEPQITWFKNNHKIQQEPGIILGPGSSTLFIER
VTEEDEGVYHCKATNQKGSVESSAYLTVQGTSDKSNLELITLTCTCVAATLFWLLLTLFI
RKMKRSSSEIKTDYLSIIMDPDEVPLDEQCERLPYDASKWEFARERLKLGKSLGRGAFGK
VVQASAFGIKKSPTCRTVAVKMLKEGATASEYKALMTELKILTHIGHHLNVVNLLGACTK
QGGPLMVIVEYCKYGNLSNYLKSKRDLFFLNKDAALHMEPKKEKMEPGLEQGKKPRLDSV
TSSESFASSGFQEDKSLSDVEEEEDSDGFYKEPITMEDLISYSFQVARGMEFLSSRKCIH
RDLAARNILLSENNVVKICDFGLARDIYKNPDYVRKGDTRLPLKWMAPESIFDKIYSTKS
DVWSYGVLLWEIFSLGGSPYPGVQMDEDFCSRLREGMRMRAPEYSTPEIYQIMLDCWHRD
PKERPRFAELVEKLGDLLQANVQQDGKDYIPINAILTGNSGFTYSTPAFSEDFFKESISA
PKFNSGSSDDVRYVNAFKFMSLERIKTFEELLPNATSMFDDYQGDSSTLLASPMLKRFTW
TDSKPKASLKIDLRVTSKSKESGLSDVSRPSFCHSSCGHVSEGKRRFTYDHAELERKIAC
CSPPPDYNSVVLYSTPPI
Target Type
Successful
Target Bioclass
Enzyme
Family
Protein kinase superfamily, Tyr protein kinase family, CSF-1/PDGF receptor subfamily
Subcellular location
Secreted; Cell membrane; Cytoplasm
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. {|Ref.11}.; [Isoform 1]: Phosphorylates PLCG.; [Isoform 2]: May function as decoy receptor for VEGFA.; [Isoform 3]: May function as decoy receptor for VEGFA.; [Isoform 4]: May function as decoy receptor for VEGFA.; [Isoform 7]: Has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.
TTD ID
T80782
Uniprot ID
P17948
DrugMap ID
TT2Q6G1
Ensemble ID
ENST00000282397.9
HGNC ID
HGNC:3763
ChEMBL ID
CHEMBL1868

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
22RV1 SNV: p.C480R .
CCK81 SNV: p.V1214A .
DU145 Deletion: p.L583YfsTer42 .
HCC70 SNV: p.I623M .
HT115 SNV: p.S62F .
J82 SNV: p.L1061V .
JURKAT SNV: p.S1077N .
KATOIII SNV: p.Q1243K .
KURAMOCHI SNV: p.L563W .
LN229 SNV: p.P143S .
LNCaP clone FGC SNV: p.S62P .
MDAMB453 SNV: p.S788F .
MEWO SNV: p.E33K; p.P460S; p.S1190F .
MFE319 Insertion: p.M609NfsTer5
SNV: p.T654A
.
NCIH146 SNV: p.E1230K .
ONS76 SNV: p.E973K .
SJSA1 SNV: p.N425H .
SNU423 SNV: p.E789K .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info 
K831(0.40)  LDD0277  [1]
DBIA
 Probe Info 
C898(1.19)  LDD1507  [2]
NAIA_4
 Probe Info 
N.A.  LDD2226  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HEK-293T C898(1.19)  LDD1507  [2]
 LDCM0226  AC11 HEK-293T C898(0.94)  LDD1509  [2]
 LDCM0276  AC17 HEK-293T C898(1.13)  LDD1515  [2]
 LDCM0278  AC19 HEK-293T C898(0.93)  LDD1517  [2]
 LDCM0281  AC21 HEK-293T C898(0.96)  LDD1520  [2]
 LDCM0285  AC25 HEK-293T C898(1.13)  LDD1524  [2]
 LDCM0287  AC27 HEK-293T C898(0.89)  LDD1526  [2]
 LDCM0289  AC29 HEK-293T C898(1.04)  LDD1528  [2]
 LDCM0290  AC3 HEK-293T C898(1.06)  LDD1529  [2]
 LDCM0294  AC33 HEK-293T C898(1.09)  LDD1533  [2]
 LDCM0296  AC35 HEK-293T C898(1.04)  LDD1535  [2]
 LDCM0298  AC37 HEK-293T C898(1.03)  LDD1537  [2]
 LDCM0303  AC41 HEK-293T C898(1.06)  LDD1542  [2]
 LDCM0305  AC43 HEK-293T C898(1.03)  LDD1544  [2]
 LDCM0307  AC45 HEK-293T C898(1.01)  LDD1546  [2]
 LDCM0311  AC49 HEK-293T C898(1.17)  LDD1550  [2]
 LDCM0312  AC5 HEK-293T C898(0.89)  LDD1551  [2]
 LDCM0314  AC51 HEK-293T C898(1.06)  LDD1553  [2]
 LDCM0316  AC53 HEK-293T C898(1.01)  LDD1555  [2]
 LDCM0320  AC57 HEK-293T C898(1.07)  LDD1559  [2]
 LDCM0322  AC59 HEK-293T C898(1.07)  LDD1561  [2]
 LDCM0325  AC61 HEK-293T C898(1.02)  LDD1564  [2]
 LDCM0248  AKOS034007472 HEK-293T C898(1.13)  LDD1511  [2]
 LDCM0356  AKOS034007680 HEK-293T C898(1.09)  LDD1570  [2]
 LDCM0404  CL17 HEK-293T C898(1.45)  LDD1608  [2]
 LDCM0406  CL19 HEK-293T C898(1.00)  LDD1610  [2]
 LDCM0409  CL21 HEK-293T C898(1.07)  LDD1613  [2]
 LDCM0417  CL29 HEK-293T C898(0.99)  LDD1621  [2]
 LDCM0420  CL31 HEK-293T C898(1.03)  LDD1624  [2]
 LDCM0422  CL33 HEK-293T C898(1.34)  LDD1626  [2]
 LDCM0431  CL41 HEK-293T C898(1.02)  LDD1635  [2]
 LDCM0433  CL43 HEK-293T C898(1.04)  LDD1637  [2]
 LDCM0435  CL45 HEK-293T C898(0.64)  LDD1639  [2]
 LDCM0440  CL5 HEK-293T C898(1.29)  LDD1644  [2]
 LDCM0444  CL53 HEK-293T C898(1.04)  LDD1647  [2]
 LDCM0446  CL55 HEK-293T C898(1.19)  LDD1649  [2]
 LDCM0448  CL57 HEK-293T C898(1.18)  LDD1651  [2]
 LDCM0457  CL65 HEK-293T C898(1.21)  LDD1660  [2]
 LDCM0459  CL67 HEK-293T C898(0.98)  LDD1662  [2]
 LDCM0461  CL69 HEK-293T C898(0.99)  LDD1664  [2]
 LDCM0462  CL7 HEK-293T C898(1.21)  LDD1665  [2]
 LDCM0470  CL77 HEK-293T C898(1.16)  LDD1673  [2]
 LDCM0472  CL79 HEK-293T C898(0.99)  LDD1675  [2]
 LDCM0475  CL81 HEK-293T C898(1.07)  LDD1678  [2]
 LDCM0483  CL89 HEK-293T C898(1.19)  LDD1686  [2]
 LDCM0484  CL9 HEK-293T C898(1.14)  LDD1687  [2]
 LDCM0486  CL91 HEK-293T C898(1.13)  LDD1689  [2]
 LDCM0488  CL93 HEK-293T C898(1.05)  LDD1691  [2]

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
2 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
3 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264