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Protein Page:
VEGFR3 (human)

Overview
VEGFR3 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3- kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr- 185', and of AKT1 at 'Ser-473'. Interacts with VEGFC and VEGFD. Monomer in the absence of bound VEGFC or VEGFD. Homodimer in the presence of bound VEGFC or VEGFD. Can also form a heterodimer with KDR. Interacts with PTPN14; the interaction is enhanced by stimulation with VEGFC. Interacts with CRK, GRB2, PTK2/FAK1, SHC1, PIK3R1 and PTPN11/SHP- 2. Identified in a complex with SRC and ITGB1. Detected in endothelial cells. Widely expressed. Detected in fetal spleen, lung and brain. Detected in adult liver, muscle, thymus, placenta, lung, testis, ovary, prostate, heart, and kidney. Present in an inactive conformation in the absence of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by MAZ51. Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Protein kinase, tyrosine (receptor); Protein kinase, TK; EC 2.7.10.1; EC 2.7.1.112; Kinase, protein; Membrane protein, integral; TK group; VEGFR family
Cellular Component: integral to plasma membrane; cytoplasm; plasma membrane; extracellular region; nucleus; receptor complex
Molecular Function: vascular endothelial growth factor receptor activity; protein binding; growth factor binding; transmembrane receptor protein tyrosine kinase activity; protein phosphatase binding; ATP binding
Biological Process: peptidyl-tyrosine phosphorylation; protein amino acid autophosphorylation; positive regulation of JNK cascade; vasculature development; positive regulation of MAPKKK cascade; positive regulation of cell proliferation; lymphangiogenesis; blood vessel morphogenesis; positive regulation of endothelial cell proliferation; positive regulation of protein amino acid phosphorylation; sprouting angiogenesis; vascular endothelial growth factor receptor signaling pathway; lymph vessel development; transmembrane receptor protein tyrosine kinase signaling pathway; negative regulation of apoptosis
Reference #:  P35916 (UniProtKB)
Alt. Names/Synonyms: FLT-4; FLT4; FLT41; Fms-like tyrosine kinase 4; fms-related tyrosine kinase 4; LMPH1A; PCL; soluble VEGFR3 variant 1; soluble VEGFR3 variant 2; soluble VEGFR3 variant 3; Tyrosine-protein kinase receptor FLT4; Vascular endothelial growth factor receptor 3; VEGFR-3; VEGFR3; VGFR3
Gene Symbols: FLT4
Molecular weight: 152,757 Da
Basal Isoelectric point: 5.9  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

VEGFR3

Protein Structure Not Found.


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Sites Implicated In
apoptosis, inhibited: Y1063‑p
cell growth, induced: Y1230‑p, Y1231‑p, Y1337‑p
cell motility, induced: Y1230‑p, Y1231‑p, Y1337‑p
enzymatic activity, induced: Y1063‑p, Y1230‑p, Y1231‑p, Y1337‑p
molecular association, regulation: Y1063‑p, Y1230‑p, Y1231‑p, Y1337‑p

Modification Sites and Domains  

Modification Sites in Parent Protein, Orthologs, and Isoforms  
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 T517-p FVEGKNKtVSKLVIQ
1 0 Y830-p PLEEQCEyLSyDASQ
1 0 Y833-p EQCEyLSyDASQWEF
1 0 Y853-p HLGRVLGyGAFGKVV
0 2 S863-p FGKVVEAsAFGIHKG
0 1 S871-p AFGIHKGsSCDTVAV
0 1 T886-p KMLKEGAtASEHRAL
0 2 S953 FSPCAEKSPEQRGRF
0 1 S976-p LDRRRPGsSDRVLFA
0 1 S986-p RVLFARFsKTEGGAR
2 104 Y1063-p FGLARDIyKDPDyVR
1 108 Y1068-p DIyKDPDyVRKGSAR
0 1 S1163-p PKARPAFsELVEILG
2 1 Y1230-p RHSLAARyyNWVsFP
2 1 Y1231-p HSLAARyyNWVsFPG
0 11 S1235-p ARyyNWVsFPGCLAR
1 0 Y1265 FPMTPTTYKGSVDNQ
3 0 Y1333-p ARGGQVFyNSEyGEL
4 2 Y1337-p QVFyNSEyGELSEPS
2 0 Y1363 TFFTDNSY_______
3817 : Phospho-VEGF Receptor 2 (Tyr1059) (D5A6) Rabbit mAb
  mouse

 
T517 FVEGKNKTVSKLVIQ
Y830 PLEEQCEYLSYDASQ
Y833 EQCEYLSYDASQWEF
H853 HLGRVLGHGAFGKVV
S863 FGKVVEASAFGINKG
S871 AFGINKGSSCDTVAV
T886 KMLKEGATASEHRAL
S953-p FNPYAEKsPEQRRRF
S976 ADRRRPGSSDRALFT
L986 RALFTRFLMGKGSAR
Y1063-p FGLARDIyKDPDyVR
Y1068-p DIyKDPDyVRKGSAR
S1163 PKARPAFSDLVEILG
Y1230-p CHSLAARyyNCVSFP
Y1231-p HSLAARyyNCVSFPG
S1235 ARyyNCVSFPGRLAR
Y1265-p LPMTPTTyKASMDNQ
Y1333-p AQGGKVFyNNEyGEV
Y1337-p KVFyNNEyGEVSQPC
Y1363-p TFFADSSy_______
3817 : Phospho-VEGF Receptor 2 (Tyr1059) (D5A6) Rabbit mAb
  rat

 
T517 SVEGKNKTVSKLVIQ
Y830 PLEEQCEYLSYDVSQ
Y833 EQCEYLSYDVSQWEF
H853 HLGRVLGHGAFGKVV
S863 FGKVVEASAFGINKG
S871 AFGINKGSSCDTVAV
T886 KMLKEGATASEHRAL
S953 FDPYAEKSPEQRRRF
S976 ADRRRLGSTDRALFT
L986 RALFTRFLMGKGSAR
Y1063-p FGLARDIyKDPDyVR
Y1068-p DIyKDPDyVRKGSAR
S1163 PKARPAFSDLVEILG
Y1230 CHSLAARYYNCVSFP
Y1231 HSLAARYYNCVSFPG
S1235 ARYYNCVSFPGRLVR
Y1265 LPMTPTTYKASVDNQ
Y1333 AQGGKVFYNNEYGEV
Y1337 KVFYNNEYGEVSQPC
Y1363 TFFADSNY_______
3817 : Phospho-VEGF Receptor 2 (Tyr1059) (D5A6) Rabbit mAb
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