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vascular endothelial growth factor C; VEGF-C; vascular endothelial growth factor-related protein; VRP; Flt4 ligand; Flt4-L (VEGFC)
Function:
- growth factor active in angiogenesis, & endothelial cell growth
- stimulates endothelial cell proliferation & migration
- has effects on the permeability of blood vessels
- may function in angiogenesis of the venous & lymphatic vascular systems during embryogenesis, & in the maintenance of differentiated lymphatic endothelium in adults
- binds & activates VEGFR-2 receptor (Flk1) & VEGFR-3 receptor (Flt4)
- macrophage secretion of VEGF-C is stimulated by NFAT5 (TonEBP) that is produced in response to hypertonic conditions [3]
- undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3, but only the fully processed activates VEGFR-2
- forms an antiparallel homodimer linked by disulfide bonds
- before secretion, a cleavage occurs between Arg-227 & Ser-228 producing an heterotetramer
- the next extracellular step of the processing removes the N-terminal propeptide
- finally the mature VEGF-C is composed mostly of two VEGF homology domains (VHDs) bound by non-covalent interactions
Structure:
- homodimer; non-covalent & antiparallel
- belongs to the PDGF/VEGF growth factor family
Compartment: secreted
Expression:
- spleen, lymph node, thymus, appendix, bone marrow, heart, placenta, ovary, skeletal muscle, prostate, testis, colon & small intestine & fetal liver, lung & kidney, but not in peripheral blood lymphocyte
Pathology:
- defects in macrophage NFAT5-stimulated VEGF-C secretion may play a role in salt-sensitive hypertension
General
vascular endothelial growth factor family protein (VEGF family)
Properties
SIZE: entity length = 419 aa
MW = 47 kD
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-31}
cysteine residue {C131}
MODIFICATION: cysteine residue {C173}
cysteine residue {C156}
MODIFICATION: cysteine residue {C-INTERCHAIN}
cysteine residue {C162}
MODIFICATION: cysteine residue {C209}
cysteine residue {C165}
MODIFICATION: cysteine residue {C-INTERCHAIN}
cysteine residue {C166}
MODIFICATION: cysteine residue {C211}
cysteine residue {C173}
MODIFICATION: cysteine residue {C131}
N-glycosylation site {N175}
N-glycosylation site {N205}
cysteine residue {C209}
MODIFICATION: cysteine residue {C162}
cysteine residue {C211}
MODIFICATION: cysteine residue {C166}
N-glycosylation site {N240}
repeats {280-362}
MOTIF: consensus repeat {280-295}
consensus repeat {304-319}
consensus repeat {328-343}
consensus repeat {347-362}
Database Correlations
OMIM 601528
UniProt P49767
PFAM correlations
Entrez Gene 7424
Kegg hsa:7424
References
- UniProt :accession P49767
- Entrez Gene :accession 7424
- Machnik A et al
Macrophages regulate salt-dependent volume and blood pressure
by a vascular endothelial growth factor-C dependent buffering
mechanism.
Nat Med 2009 May; 15:545
PMID: 19412173