VEGF165 (VEGFA) Active Protein

This gene is a member of the PDGF/VEGF growth factor family and encodes a protein that is often found as a disulfide linked homodimer. This protein is a glycosylated mitogen that specifically acts on endothelial cells and has various effects, including mediating increased vascular permeability, inducing angiogenesis, vasculogenesis and endothelial cell growth, promoting cell migration, and inhibiting apoptosis. Elevated levels of this protein is linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy. Alternatively spliced transcript variants, encoding either freely secreted or cell-associated isoforms, have been characterized. There is also evidence for the use of non-AUG (CUG) translation initiation sites upstream of, and in-frame with the first AUG, leading to additional isoforms. [provided by RefSeq, Jul 2008]

VEGF iso14: 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. Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1). These are 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. Belongs to the PDGF/VEGF growth factor family. 13 isoforms of the human protein are produced by alternative promoter.

Protein type: Secreted; Secreted, signal peptide; Cytokine; Motility/polarity/chemotaxis

Chromosomal Location of Human Ortholog: 6p12

Cellular Component: proteinaceous extracellular matrix; extracellular space; cell surface; membrane; cytoplasm; extracellular region; secretory granule

Molecular Function: heparin binding; identical protein binding; protein homodimerization activity; growth factor activity; extracellular matrix binding; platelet-derived growth factor receptor binding; cytokine activity; vascular endothelial growth factor receptor 1 binding; vascular endothelial growth factor receptor binding; receptor agonist activity; protein binding; vascular endothelial growth factor receptor 2 binding; protein heterodimerization activity; fibronectin binding; chemoattractant activity

Biological Process: heart morphogenesis; positive regulation of positive chemotaxis; positive regulation of cell adhesion; macrophage differentiation; positive regulation of leukocyte migration; positive regulation of receptor internalization; cell maturation; basophil chemotaxis; positive regulation of MAP kinase activity; regulation of cell shape; positive chemotaxis; positive regulation of mesenchymal cell proliferation; mesoderm development; kidney development; nervous system development; platelet activation; positive regulation of neuroblast proliferation; monocyte differentiation; positive regulation of blood vessel endothelial cell migration; activation of CREB transcription factor; positive regulation of protein amino acid autophosphorylation; positive regulation of vascular permeability; regulation of transcription from RNA polymerase II promoter; patterning of blood vessels; eye photoreceptor cell development; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of angiogenesis; camera-type eye morphogenesis; cell migration during sprouting angiogenesis; branching morphogenesis of a tube; cardiac muscle fiber development; positive regulation of cell division; positive regulation of axon extension involved in axon guidance; activation of protein kinase activity; positive regulation of endothelial cell proliferation; positive regulation of transcription from RNA polymerase II promoter; regulation of cGMP metabolic process; surfactant homeostasis; positive regulation of epithelial cell proliferation; negative regulation of apoptosis; lactation; post-embryonic camera-type eye development; negative regulation of transcription from RNA polymerase II promoter; negative regulation of caspase activity; positive regulation of vascular endothelial growth factor receptor signaling pathway; induction of positive chemotaxis; platelet degranulation; positive regulation of focal adhesion formation; ovarian follicle development; epithelial cell differentiation; positive regulation of cell proliferation; angiogenesis; vasculogenesis; in utero embryonic development; lumen formation; positive regulation of cell motility; positive regulation of peptidyl-serine phosphorylation; positive regulation of protein complex assembly; response to hypoxia; artery morphogenesis; positive regulation of protein amino acid phosphorylation; vascular endothelial growth factor receptor signaling pathway; blood coagulation; positive regulation of cell migration; growth; lung development

Disease: Microvascular Complications Of Diabetes, Susceptibility To, 1