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DrugBank target: P35916

DrugBank target: P35916 (VGFR3_HUMAN)     

Example structure of target: 4bsj

( There are 2 structures corresponding to this UniProt sequence in the PDB. Click the orange, plus icon above for a list. )

Vascular endothelial growth factor receptor 3

Fms-like tyrosine kinase 4, Tyrosine-protein kinase receptor FLT4, VEGFR-3, FLT-4.

Function

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'..

Enzyme

2.7.10.1   [EC->PDB]   [IntEnz]   [ExPASy]   [KEGG]  

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Disease(s)

Lymphedema, hereditary, 1A (LMPH1A) [MIM:153100]: A chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections and physical impairment. Note=The disease is caused by mutations affecting the gene represented in this entry.
Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Note=Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases.

Schematic diagram of Pfam domains in target sequence plus wiring diagrams of PDB structures of target.

4bsj
4bsk
4bsj
4bsk

Key:    PfamA domain

Sequence length: 1362 a.a.

Approved drugs targeting this protein

The DrugBank database identifies 5 drugs for this target protein:

 

Generic name: DB00398 sorafenib
BAX
Formula: C21H16Clf3N4O3
Structure: There are 6 PDB structures containing this molecule although none are bound to the above target protein.
 
Generic name: DB06589 pazopanib
Formula: C21H23N7O2S
Structure: There are no structures of this molecule in the PDB.
Generic name: DB06626 axitinib
AXI
Formula:
Structure: There are 2 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB01268 sunitinib
B49
Formula: C22H27Fn4O2
Structure: There are 7 PDB structures containing this molecule although none are bound to the above target protein.
 
Generic name: DB08896 regorafenib
Formula: C21H15Clf4N4O3
Structure: There are no structures of this molecule in the PDB.

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