VEGF
This gene is a member of the PDGF/VEGF growth factor family. It encodes a heparin-binding protein, which exists as a disulfide-linked homodimer. This growth factor induces proliferation and migration of vascular endothelial cells, and is essential for both physiological and pathological angiogenesis. Disruption of this gene in mice resulted in abnormal embryonic blood vessel formation. This gene is upregulated in many known tumors and its expression is correlated with tumor stage and progression. Elevated levels of this protein are found in patients with POEMS syndrome, also known as Crow-Fukase syndrome. Allelic variants of this gene have been associated with microvascular complications of diabetes 1 (MVCD1) and atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been described. There is also evidence for alternative translation initiation from upstream non-AUG (CUG) codons resulting in additional isoforms. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is antiangiogenic. Expression of some isoforms derived from the AUG start codon is regulated by a small upstream open reading frame, which is located within an internal ribosome entry site.
Full Name
vascular endothelial growth factor A
Function
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth. Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity).
Also binds the DEAR/FBXW7-AS1 receptor (PubMed:17446437).
Biological Process
Biological Process activation of protein kinase activity Source:BHF-UCL2 Publications
Biological Process angiogenesis Source:UniProtKB2 Publications
Biological Process artery morphogenesis Source:BHF-UCL
Biological Process basophil chemotaxis Source:UniProtKB
Biological Process branching involved in blood vessel morphogenesis Source:BHF-UCL2 Publications
Biological Process camera-type eye morphogenesis Source:BHF-UCL
Biological Process cardiac muscle cell development Source:BHF-UCL
Biological Process cardiac vascular smooth muscle cell development Source:BHF-UCL
Biological Process cell maturation Source:BHF-UCL
Biological Process cell migration involved in sprouting angiogenesis Source:BHF-UCL2 Publications
Biological Process cellular response to hypoxia Source:MGI1 Publication
Biological Process cellular response to vascular endothelial growth factor stimulus Source:BHF-UCL2 Publications
Biological Process cellular stress response to acid chemical Source:BHF-UCL1 Publication
Biological Process commissural neuron axon guidance Source:BHF-UCL
Biological Process coronary artery morphogenesis Source:BHF-UCL
Biological Process coronary vein morphogenesis Source:BHF-UCL
Biological Process dopaminergic neuron differentiation Source:BHF-UCL
Biological Process endothelial cell chemotaxis Source:BHF-UCL1 Publication
Biological Process epithelial cell differentiation Source:BHF-UCL
Biological Process eye photoreceptor cell development Source:BHF-UCL
Biological Process heart morphogenesis Source:BHF-UCL
Biological Process in utero embryonic development Source:BHF-UCL
Biological Process induction of positive chemotaxis Source:UniProtKB1 Publication
Biological Process kidney development Source:BHF-UCL
Biological Process lactation Source:BHF-UCL
Biological Process lung development Source:BHF-UCL
Biological Process lymph vessel morphogenesis Source:BHF-UCL
Biological Process macrophage differentiation Source:DFLAT1 Publication
Biological Process mammary gland alveolus development Source:BHF-UCL
Biological Process mesoderm development Source:BHF-UCL
Biological Process monocyte differentiation Source:DFLAT1 Publication
Biological Process motor neuron migration Source:UniProtKB
Biological Process negative regulation of adherens junction organization Source:ARUK-UCL1 Publication
Biological Process negative regulation of apoptotic process Source:UniProtKB2 Publications
Biological Process negative regulation of blood-brain barrier permeability Source:ARUK-UCL1 Publication
Biological Process negative regulation of cell-cell adhesion mediated by cadherin Source:ARUK-UCL1 Publication
Biological Process negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source:UniProtKB1 Publication
Biological Process negative regulation of establishment of endothelial barrier Source:ARUK-UCL1 Publication
Biological Process negative regulation of gene expression Source:BHF-UCL1 Publication
Biological Process negative regulation of transcription by RNA polymerase II Source:BHF-UCL1 Publication
Biological Process nervous system development Source:UniProtKB1 Publication
Biological Process outflow tract morphogenesis Source:BHF-UCL
Biological Process ovarian follicle development Source:BHF-UCL
Biological Process positive chemotaxis Source:BHF-UCL1 Publication
Biological Process positive regulation of angiogenesis Source:BHF-UCL1 Publication
Biological Process positive regulation of axon extension involved in axon guidance Source:BHF-UCL
Biological Process positive regulation of blood vessel endothelial cell migration Source:BHF-UCL3 Publications
Biological Process positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis Source:ARUK-UCL1 Publication
Biological Process positive regulation of branching involved in ureteric bud morphogenesis Source:BHF-UCL
Biological Process positive regulation of cell adhesion Source:UniProtKB1 Publication
Biological Process positive regulation of cell division Source:UniProtKB-KW
Biological Process positive regulation of cell migration Source:BHF-UCL2 Publications
Biological Process positive regulation of cell migration by vascular endothelial growth factor signaling pathway Source:BHF-UCL
Biological Process positive regulation of cell migration involved in sprouting angiogenesis Source:BHF-UCL1 Publication
Biological Process positive regulation of cell population proliferation Source:BHF-UCL1 Publication
Biological Process positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway Source:BHF-UCL1 Publication
Biological Process positive regulation of cold-induced thermogenesis Source:YuBioLabBy Similarity
Biological Process positive regulation of CREB transcription factor activity Source:BHF-UCL1 Publication
Biological Process positive regulation of DNA biosynthetic process Source:UniProtKB
Biological Process positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway Source:BHF-UCL3 Publications
Biological Process positive regulation of endothelial cell migration Source:BHF-UCL1 Publication
Biological Process positive regulation of endothelial cell proliferation Source:BHF-UCL2 Publications
Biological Process positive regulation of epithelial cell proliferation Source:BHF-UCL
Biological Process positive regulation of epithelial tube formation Source:BHF-UCL
Biological Process positive regulation of ERK1 and ERK2 cascade Source:BHF-UCL
Biological Process positive regulation of focal adhesion assembly Source:UniProtKB1 Publication
Biological Process positive regulation of gene expression Source:BHF-UCL1 Publication
Biological Process positive regulation of histone deacetylase activity Source:BHF-UCL1 Publication
Biological Process positive regulation of leukocyte migration Source:BHF-UCL1 Publication
Biological Process positive regulation of MAP kinase activity Source:BHF-UCL1 Publication
Biological Process positive regulation of MAPK cascade Source:BHF-UCL
Biological Process positive regulation of mast cell chemotaxis Source:UniProtKB1 Publication
Biological Process positive regulation of neuroblast proliferation Source:BHF-UCL
Biological Process positive regulation of p38MAPK cascade Source:UniProtKB1 Publication
Biological Process positive regulation of peptidyl-serine phosphorylation Source:BHF-UCL2 Publications
Biological Process positive regulation of peptidyl-tyrosine autophosphorylation Source:BHF-UCL1 Publication
Biological Process positive regulation of peptidyl-tyrosine phosphorylation Source:BHF-UCL1 Publication
Biological Process positive regulation of phosphatidylinositol 3-kinase signaling Source:BHF-UCL
Biological Process positive regulation of phosphorylation Source:BHF-UCL
Biological Process positive regulation of positive chemotaxis Source:BHF-UCL2 Publications
Biological Process positive regulation of protein autophosphorylation Source:BHF-UCL1 Publication
Biological Process positive regulation of protein kinase B signaling Source:BHF-UCL
Biological Process positive regulation of protein kinase C signaling Source:BHF-UCL1 Publication
Biological Process positive regulation of protein kinase D signaling Source:BHF-UCL1 Publication
Biological Process positive regulation of protein localization to early endosome Source:BHF-UCL
Biological Process positive regulation of protein phosphorylation Source:UniProtKB2 Publications
Biological Process positive regulation of protein-containing complex assembly Source:UniProtKB2 Publications
Biological Process positive regulation of receptor internalization Source:BHF-UCL1 Publication
Biological Process positive regulation of retinal ganglion cell axon guidance Source:BHF-UCL
Biological Process positive regulation of sprouting angiogenesis Source:BHF-UCL1 Publication
Biological Process positive regulation of transcription by RNA polymerase II Source:BHF-UCL1 Publication
Biological Process positive regulation of transcription from RNA polymerase II promoter in response to hypoxia Source:BHF-UCL1 Publication
Biological Process positive regulation of trophoblast cell migration Source:BHF-UCL1 Publication
Biological Process positive regulation of vascular endothelial growth factor signaling pathway Source:ComplexPortal1 Publication
Biological Process positive regulation of vascular permeability Source:ARUK-UCL1 Publication
Biological Process post-embryonic camera-type eye development Source:BHF-UCL
Biological Process primitive erythrocyte differentiation Source:BHF-UCL
Biological Process regulation of cell shape Source:BHF-UCL2 Publications
Biological Process regulation of nitric oxide mediated signal transduction Source:MGI1 Publication
Biological Process regulation of retinal ganglion cell axon guidance Source:BHF-UCL
Biological Process regulation of transcription by RNA polymerase II Source:BHF-UCL
Biological Process response to hypoxia Source:UniProtKB1 Publication
Biological Process sprouting angiogenesis Source:GO_Central1 Publication
Biological Process surfactant homeostasis Source:BHF-UCL
Biological Process tube formation Source:UniProtKB1 Publication
Biological Process vascular endothelial growth factor receptor signaling pathway Source:BHF-UCL3 Publications
Biological Process vascular endothelial growth factor receptor-2 signaling pathway Source:BHF-UCL1 Publication
Biological Process vascular endothelial growth factor signaling pathway Source:UniProtKB1 Publication
Biological Process vascular wound healing Source:BHF-UCL1 Publication
Biological Process vasculogenesis Source:UniProtKB1 Publication
Biological Process VEGF-activated neuropilin signaling pathway Source:BHF-UCL
Cellular Location
Secreted
VEGF121 is acidic and freely secreted. VEGF165 is more basic, has heparin-binding properties and, although a significant proportion remains cell-associated, most is freely secreted. VEGF189 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix, although it may be released as a soluble form by heparin, heparinase or plasmin.
Involvement in disease
Microvascular complications of diabetes 1 (MVCD1):
Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.