lmmol · Proteins

Vascular endothelial growth factor receptor 3

UniProt P35916 Organism Homo sapiens Gene FLT4, VEGFR3 EC 2.7.10.1

Also known as: FLT4, VEGFR3

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'.

Classification

Family (Pfam)
PF07679 I-set, PF13927 Ig_3, PF22971 Ig_VEGFR-1-like_5th, PF07714 PK_Tyr_Ser-Thr, PF21339 VEGFR-1-like_Ig-like, PF17988 VEGFR-2_TMD, PF22854 VEGFR1-3_N_Ig-like
InterPro
Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_I-set, Ig_sub, Ig_sub2, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS, VEGFR-2_TMD, VEGFR1-3_5th, VEGFR1-3_N_Ig-like
Functional cluster
Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 2

A predicted model is available from AlphaFold.

Gene Ontology · 34

Disease associations

Drugs targeting this protein · 43

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 45 cited papers

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