Names & Taxonomy
- Uniprot ID:
- P35916
- Entry Name:
- VGFR3_HUMAN
- Status:
- reviewed
- Protein Names:
- Vascular endothelial growth factor receptor 3 (VEGFR-3) (EC 2.7.10.1) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4)
- Gene Names:
- FLT4 VEGFR3
- Gene Names Primary:
- FLT4
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 1363
- Sequence:
- MQRGAALCLRLWLCLGLLDGLVSGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNELYDIQLLPRKSLELLVGEKLVLNCTVWAEFNSGVTFDWDYPGKQAERGKWVPERRSQQTHTELSSILTIHNVSQHDLGSYVCKANNGIQRFRESTEVIVHENPFISVEWLKGPILEATAGDELVKLPVKLAAYPPPEFQWYKDGKALSGRHSPHALVLKEVTEASTGTYTLALWNSAAGLRRNISLELVVNVPPQIHEKEASSPSIYSRHSRQALTCTAYGVPLPLSIQWHWRPWTPCKMFAQRSLRRRQQQDLMPQCRDWRAVTTQDAVNPIESLDTWTEFVEGKNKTVSKLVIQNANVSAMYKCVVSNKVGQDERLIYFYVTTIPDGFTIESKPSEELLEGQPVLLSCQADSYKYEHLRWYRLNLSTLHDAHGNPLLLDCKNVHLFATPLAASLEEVAPGARHATLSLSIPRVAPEHEGHYVCEVQDRRSHDKHCHKKYLSVQALEAPRLTQNLTDLLVNVSDSLEMQCLVAGAHAPSIVWYKDERLLEEKSGVDLADSNQKLSIQRVREEDAGRYLCSVCNAKGCVNSSASVAVEGSEDKGSMEIVILVGTGVIAVFFWVLLLLIFCNMRRPAHADIKTGYLSIIMDPGEVPLEEQCEYLSYDASQWEFPRERLHLGRVLGYGAFGKVVEASAFGIHKGSSCDTVAVKMLKEGATASEHRALMSELKILIHIGNHLNVVNLLGACTKPQGPLMVIVEFCKYGNLSNFLRAKRDAFSPCAEKSPEQRGRFRAMVELARLDRRRPGSSDRVLFARFSKTEGGARRASPDQEAEDLWLSPLTMEDLVCYSFQVARGMEFLASRKCIHRDLAARNILLSESDVVKICDFGLARDIYKDPDYVRKGSARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFCQRLRDGTRMRAPELATPAIRRIMLNCWSGDPKARPAFSELVEILGDLLQGRGLQEEEEVCMAPRSSQSSEEGSFSQVSTMALHIAQADAEDSPPSLQRHSLAARYYNWVSFPGCLARGAETRGSSRMKTFEEFPMTPTTYKGSVDNQTDSGMVLASEEFEQIESRHRQESGFSCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane; Single-pass type I membrane protein. Cytoplasm. Nucleus. Note=Ligand-mediated autophosphorylation leads to rapid internalization.; Isoform 1: Cell membrane; Single-pass type I membrane protein. Note=Ligand-mediated autophosphorylation leads to rapid internalization.; Isoform 2: Cell membrane; Single-pass type I membrane protein.; Isoform 3: Secreted. Cytoplasm.
Function
- 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'.
- Catalytic Activity:
- ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
- Enzyme Regulation:
- ENZYME REGULATION: 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.
- Active Site:
- ACT_SITE 1037 1037 Proton acceptor.
- Cross Reference Drug Bank:
- DB06626 DB09078 DB09079 DB06589 DB08896 DB00398 DB01268
- Gene Ontology Go:
- cytoplasm
extracellular region
integral component of plasma membrane
nucleus
plasma membrane
receptor complex
ATP binding
growth factor binding
protein phosphatase binding
transmembrane receptor protein tyrosine kinase activity
vascular endothelial growth factor-activated receptor activity
blood vessel morphogenesis
cellular response to vascular endothelial growth factor stimulus
lymph vessel development
lymphangiogenesis
negative regulation of apoptotic process
peptidyl-tyrosine phosphorylation
positive regulation of cell proliferation
positive regulation of endothelial cell migration
positive regulation of endothelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of JNK cascade
positive regulation of MAPK cascade
positive regulation of protein kinase C signaling
positive regulation of protein phosphorylation
positive regulation of vascular endothelial growth factor production
protein autophosphorylation
regulation of blood vessel remodeling
sprouting angiogenesis
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
vascular endothelial growth factor signaling pathway
vasculature development - Gene Ontology Biological Process:
- blood vessel morphogenesis
cellular response to vascular endothelial growth factor stimulus
lymphangiogenesis
lymph vessel development
negative regulation of apoptotic process
peptidyl-tyrosine phosphorylation
positive regulation of cell proliferation
positive regulation of endothelial cell migration
positive regulation of endothelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of JNK cascade
positive regulation of MAPK cascade
positive regulation of protein kinase C signaling
positive regulation of protein phosphorylation
positive regulation of vascular endothelial growth factor production
protein autophosphorylation
regulation of blood vessel remodeling
sprouting angiogenesis
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
vascular endothelial growth factor signaling pathway
vasculature development - Gene Ontology Molecular Function:
- ATP binding
growth factor binding
protein phosphatase binding
transmembrane receptor protein tyrosine kinase activity
vascular endothelial growth factor-activated receptor activity - Gene Ontology Cellular Component:
- cytoplasm
extracellular region
integral component of plasma membrane
nucleus
plasma membrane
receptor complex - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Angiogenesis
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Disulfide bond
Glycoprotein
Immunoglobulin domain
Kinase
Membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase - Interacts With:
- P08238; P35968; P49767
Publication
- PubMed ID:
- 1327515 1319394 8386825 8700872 18593464 14702039 15372022 1310071 7692369 15340161 7898938 7675451 9435229 11532940 12881528 15474514 15102829 16076871 16335952 16452200 17210781 19779139 19610651 20826270 20431062 20224550 20445537 21273538 18680722 19230644 21711246 21196198 9817924 10856194 10835628 11807987 16965327 16924388 17458866 17344846 19289394 26091405