The VEGFA gene and its putative association with human ageing

Cell Types

Dermal endothelial

Cell Lines

Primary cell

Cancer Cell?

No

Method

Overexpression

Type of senescence

Replicative

Senescence Effect

Inhibits

Primary Reference

Watanabe et al. (1997) Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) delays and induces escape from senescence in human dermal microvascular endothelial cells. Oncogene 14(17)2025-32 (PubMed)

HGNC symbol

VEGFA

Aliases

VEGF; VEGF-A; VPF

Common name

vascular endothelial growth factor A

Entrez Id

7422

Description

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. The levels of VEGF are increased during infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus promoting inflammation by facilitating recruitment of inflammatory cells, and by increasing the level of angiopoietin II (Ang II), one of two products of the SARS-CoV-2 binding target, angiotensin-converting enzyme 2 (ACE2). In turn, Ang II facilitates the elevation of VEGF, thus forming a vicious cycle in the release of inflammatory cytokines. [provided by RefSeq, Jun 2020].

Gene Ontology

Process:

GO:10629; negative regulation of gene expression
GO:43066; negative regulation of apoptotic process
GO:7165; signal transduction
GO:30154; cell differentiation
GO:1934; positive regulation of protein phosphorylation
GO:7399; nervous system development
GO:51781; positive regulation of cell division
GO:1525; angiogenesis
GO:8284; positive regulation of cell population proliferation
GO:45766; positive regulation of angiogenesis
GO:10628; positive regulation of gene expression
GO:1666; response to hypoxia
GO:33138; positive regulation of peptidyl-serine phosphorylation
GO:45944; positive regulation of transcription by RNA polymerase II
GO:50731; positive regulation of peptidyl-tyrosine phosphorylation
GO:1938; positive regulation of endothelial cell proliferation
GO:30335; positive regulation of cell migration
GO:43406; positive regulation of MAP kinase activity
GO:45785; positive regulation of cell adhesion
GO:122; negative regulation of transcription by RNA polymerase II
GO:10595; positive regulation of endothelial cell migration
GO:90050; positive regulation of cell migration involved in sprouting angiogenesis
GO:43154; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:48469; cell maturation
GO:120162; positive regulation of cold-induced thermogenesis
GO:31334; positive regulation of protein-containing complex assembly
GO:3151; outflow tract morphogenesis
GO:35148; tube formation
GO:1569; branching involved in blood vessel morphogenesis
GO:2042; cell migration involved in sprouting angiogenesis
GO:35767; endothelial cell chemotaxis
GO:35924; cellular response to vascular endothelial growth factor stimulus
GO:38190; VEGF-activated neuropilin signaling pathway
GO:48010; vascular endothelial growth factor receptor signaling pathway
GO:48842; positive regulation of axon extension involved in axon guidance
GO:48844; artery morphogenesis
GO:50918; positive chemotaxis
GO:71679; commissural neuron axon guidance
GO:90259; regulation of retinal ganglion cell axon guidance
GO:97475; motor neuron migration
GO:1902336; positive regulation of retinal ganglion cell axon guidance
GO:71542; dopaminergic neuron differentiation
GO:32147; activation of protein kinase activity
GO:3007; heart morphogenesis
GO:55013; cardiac muscle cell development
GO:43536; positive regulation of blood vessel endothelial cell migration
GO:1903672; positive regulation of sprouting angiogenesis
GO:1900745; positive regulation of p38MAPK cascade
GO:71456; cellular response to hypoxia
GO:1822; kidney development
GO:50930; induction of positive chemotaxis
GO:2040; sprouting angiogenesis
GO:38084; vascular endothelial growth factor signaling pathway
GO:60754; positive regulation of mast cell chemotaxis
GO:2052; positive regulation of neuroblast proliferation
GO:30324; lung development
GO:2092; positive regulation of receptor internalization
GO:1900086; positive regulation of peptidyl-tyrosine autophosphorylation
GO:1570; vasculogenesis
GO:31954; positive regulation of protein autophosphorylation
GO:50679; positive regulation of epithelial cell proliferation
GO:8360; regulation of cell shape
GO:51894; positive regulation of focal adhesion assembly
GO:38033; positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway
GO:42462; eye photoreceptor cell development
GO:50927; positive regulation of positive chemotaxis
GO:1903589; positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis
GO:38091; positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway
GO:1701; in utero embryonic development
GO:30224; monocyte differentiation
GO:30225; macrophage differentiation
GO:48593; camera-type eye morphogenesis
GO:51272; positive regulation of cellular component movement
GO:10749; regulation of nitric oxide mediated signal transduction
GO:1541; ovarian follicle development
GO:2687; positive regulation of leukocyte migration
GO:3169; coronary vein morphogenesis
GO:7498; mesoderm development
GO:7595; lactation
GO:30855; epithelial cell differentiation
GO:31077; post-embryonic camera-type eye development
GO:32793; positive regulation of CREB transcription factor activity
GO:36303; lymph vessel morphogenesis
GO:36324; vascular endothelial growth factor receptor-2 signaling pathway
GO:43117; positive regulation of vascular permeability
GO:43129; surfactant homeostasis
GO:60319; primitive erythrocyte differentiation
GO:60749; mammary gland alveolus development
GO:60948; cardiac vascular smooth muscle cell development
GO:60982; coronary artery morphogenesis
GO:61042; vascular wound healing
GO:61419; positive regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:90037; positive regulation of protein kinase C signaling
GO:90190; positive regulation of branching involved in ureteric bud morphogenesis
GO:97533; cellular stress response to acid chemical
GO:1901165; positive regulation of trophoblast cell migration
GO:1901727; positive regulation of histone deacetylase activity
GO:1903141; negative regulation of establishment of endothelial barrier
GO:1903392; negative regulation of adherens junction organization
GO:1903572; positive regulation of protein kinase D signaling
GO:1905604; negative regulation of blood-brain barrier permeability
GO:2000048; negative regulation of cell-cell adhesion mediated by cadherin
GO:14068; positive regulation of phosphatidylinositol 3-kinase signaling
GO:51897; positive regulation of protein kinase B signaling
GO:38089; positive regulation of cell migration by vascular endothelial growth factor signaling pathway
GO:1905278; positive regulation of epithelial tube formation
GO:42327; positive regulation of phosphorylation
GO:70374; positive regulation of ERK1 and ERK2 cascade
GO:6357; regulation of transcription by RNA polymerase II
GO:2000573; positive regulation of DNA biosynthetic process
GO:43410; positive regulation of MAPK cascade
GO:2575; basophil chemotaxis
GO:1902966; positive regulation of protein localization to early endosome

Cellular component:

GO:5615; extracellular space
GO:5737; cytoplasm
GO:16020; membrane
GO:5576; extracellular region
GO:31012; extracellular matrix
GO:9986; cell surface
GO:31093; platelet alpha granule lumen
GO:30141; secretory granule
GO:5912; adherens junction

Function:

GO:8083; growth factor activity
GO:5515; protein binding
GO:8201; heparin binding
GO:48018; receptor ligand activity
GO:42802; identical protein binding
GO:42803; protein homodimerization activity
GO:5125; cytokine activity
GO:42056; chemoattractant activity
GO:5172; vascular endothelial growth factor receptor binding
GO:43184; vascular endothelial growth factor receptor 2 binding
GO:5161; platelet-derived growth factor receptor binding
GO:1968; fibronectin binding
GO:43183; vascular endothelial growth factor receptor 1 binding
GO:50840; extracellular matrix binding
GO:38191; neuropilin binding

Hide GO terms

Danio rerio

vegfaa

Mus musculus

Vegfa

Rattus norvegicus

Vegfa

GenAge human genes