Vegfa encodes vascular endothelial growth factor A (VEGF-A), a secreted, glycosylated, disulfide-linked homodimeric cystine-knot growth factor of the PDGF/VEGF family. Alternative splicing produces VEGF-A120, -A144, -A164 and -A188, which differ in basic heparin/extracellular-matrix-binding domains: VEGF-A120 is freely diffusible, whereas VEGF-A164 and especially VEGF-A188 are retained on heparan sulfate and matrix. VEGF-A acts as a ligand for the receptor tyrosine kinases VEGFR1/FLT1 and VEGFR2/KDR, with neuropilin-1 and heparan sulfate as co-receptors; VEGFR2 activation drives endothelial cell proliferation, survival, migration and chemotaxis, and increases vascular permeability. It is thereby the principal inducer of vasculogenesis and angiogenesis, and is strongly induced by hypoxia. In rat it is required for postnatal lung alveolarisation and capillary growth, coronary collateral growth and ischaemia-induced vascular leak, and it also acts on non-endothelial cells, stimulating neurogenesis and neuronal survival, smooth muscle cell proliferation and Th1 polarisation of T cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Negative regulation of transcription by RNA polymerase II: distal output of VEGF signalling. Reason: VEGF-A is a secreted ligand with no transcription-regulatory activity; changes in target-gene transcription are distal consequences of receptor signalling and are better captured by the VEGFR signalling terms. The human donor (PMID:18093989) describes altered arterial/venous marker expression in Vegf120 mice. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS SOURCE BUT NOT TARGET The human source shows expression changes downstream of VEGF signalling, not a VEGF-A transcriptional activity; same scoping issue at source. Supporting Evidence: file:rat/Vegfa/Vegfa-deep-research-manual.md Transcription, mRNA-stability and gene-expression rows reflect distal signalling outputs, not activities of VEGF-A itself. |
| GO:0001525 angiogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: Angiogenesis: VEGF-A is the master angiogenic factor. Reason: Rat in vivo evidence: VEGF blockade in newborn rats causes loss of lung capillaries and VEGF gene therapy promotes lung capillary formation; VEGF is required for coronary collateral growth and drives ischaemic hindlimb neovascularisation. Core process. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries PMID:16230500 Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. |
| GO:0001525 angiogenesis | IMP PMID:16230500 Vascular endothelial growth factor gene therapy increases su... | ACCEPT | Summary: Angiogenesis: VEGF-A is the master angiogenic factor. Reason: Rat in vivo evidence: VEGF blockade in newborn rats causes loss of lung capillaries and VEGF gene therapy promotes lung capillary formation; VEGF is required for coronary collateral growth and drives ischaemic hindlimb neovascularisation. Core process. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries PMID:16230500 Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. |
| GO:0001525 angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Angiogenesis: VEGF-A is the master angiogenic factor. Reason: Rat in vivo evidence: VEGF blockade in newborn rats causes loss of lung capillaries and VEGF gene therapy promotes lung capillary formation; VEGF is required for coronary collateral growth and drives ischaemic hindlimb neovascularisation. Core process. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries PMID:16230500 Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. |
| GO:0001525 angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Angiogenesis: VEGF-A is the master angiogenic factor. Reason: Rat in vivo evidence: VEGF blockade in newborn rats causes loss of lung capillaries and VEGF gene therapy promotes lung capillary formation; VEGF is required for coronary collateral growth and drives ischaemic hindlimb neovascularisation. Core process. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries PMID:16230500 Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. |
| GO:0001525 angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Angiogenesis: VEGF-A is the master angiogenic factor. Reason: Rat in vivo evidence: VEGF blockade in newborn rats causes loss of lung capillaries and VEGF gene therapy promotes lung capillary formation; VEGF is required for coronary collateral growth and drives ischaemic hindlimb neovascularisation. Core process. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries PMID:16230500 Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. |
| GO:0001525 angiogenesis | TAS PMID:12181492 Vascular endothelial growth factor (VEGF) stimulates neuroge... | ACCEPT | Summary: Angiogenesis: VEGF-A is the master angiogenic factor. Reason: Rat in vivo evidence: VEGF blockade in newborn rats causes loss of lung capillaries and VEGF gene therapy promotes lung capillary formation; VEGF is required for coronary collateral growth and drives ischaemic hindlimb neovascularisation. Core process. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries PMID:16230500 Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. |
| GO:0001541 ovarian follicle development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ovarian follicle development (follicular/luteal angiogenesis). Reason: Ovarian follicle development (follicular/luteal angiogenesis). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0001568 blood vessel development | ISO GO_REF:0000121 | MODIFY | Summary: Blood vessel development: true but general; VEGF-A acts in vasculogenesis and angiogenesis. Reason: GO:0001525 angiogenesis is part_of/is_a descendant of blood vessel development, as is vasculogenesis (GO:0001570) (checked with OAK). VEGF-A is required for both; the general phenotype-derived term is refined to these two processes. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Mouse knockout phenotype supports the claim; only granularity is refined. Proposed replacements: angiogenesis vasculogenesis Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0001569 branching involved in blood vessel morphogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Branching involved in blood vessel morphogenesis. Reason: Heparin-binding VEGF-A isoforms set up the gradients that control vessel branching (mouse isoform-specific evidence transferred). Part of VEGF-A's core angiogenic role. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix |
| GO:0001569 branching involved in blood vessel morphogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Branching involved in blood vessel morphogenesis. Reason: Heparin-binding VEGF-A isoforms set up the gradients that control vessel branching (mouse isoform-specific evidence transferred). Part of VEGF-A's core angiogenic role. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix |
| GO:0001569 branching involved in blood vessel morphogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Branching involved in blood vessel morphogenesis. Reason: Heparin-binding VEGF-A isoforms set up the gradients that control vessel branching (mouse isoform-specific evidence transferred). Part of VEGF-A's core angiogenic role. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix |
| GO:0001666 response to hypoxia | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Response to hypoxia (hypoxia-inducible HIF target). Reason: Response to hypoxia (hypoxia-inducible HIF target). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:12881220 staurosporine, a nonselective PKC inhibitor, prevented the induction of VEGF by hypoxia PMID:12181492 Vascular endothelial growth factor (VEGF) is a hypoxia-inducible secreted protein that interacts with receptor tyrosine kinases on endothelial cells to promote angiogenesis. |
| GO:0001666 response to hypoxia | IDA PMID:12881220 Hypoxia induces myocyte-dependent COX-2 regulation in endoth... | KEEP AS NON CORE | Summary: Response to hypoxia (hypoxia-inducible HIF target). Reason: Response to hypoxia (hypoxia-inducible HIF target). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:12881220 staurosporine, a nonselective PKC inhibitor, prevented the induction of VEGF by hypoxia PMID:12181492 Vascular endothelial growth factor (VEGF) is a hypoxia-inducible secreted protein that interacts with receptor tyrosine kinases on endothelial cells to promote angiogenesis. |
| GO:0001666 response to hypoxia | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Response to hypoxia (hypoxia-inducible HIF target). Reason: Response to hypoxia (hypoxia-inducible HIF target). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:12881220 staurosporine, a nonselective PKC inhibitor, prevented the induction of VEGF by hypoxia PMID:12181492 Vascular endothelial growth factor (VEGF) is a hypoxia-inducible secreted protein that interacts with receptor tyrosine kinases on endothelial cells to promote angiogenesis. |
| GO:0001701 in utero embryonic development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: In utero embryonic development (Vegfa haploinsufficiency is embryonic lethal in mouse). Reason: In utero embryonic development (Vegfa haploinsufficiency is embryonic lethal in mouse). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0001822 kidney development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kidney development (glomerular endothelium depends on podocyte VEGF-A). Reason: Kidney development (glomerular endothelium depends on podocyte VEGF-A). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:11940521 Immunoelectron microscopy of glomeruli confirmed VEGF localization to podocytes and in the basement membrane. |
| GO:0001934 positive regulation of protein phosphorylation | ISS GO_REF:0000024 | MODIFY | Summary: Positive regulation of protein phosphorylation: correct but general; VEGF-A induces receptor tyrosine phosphorylation. Reason: VEGF-A induces ligand-dependent autophosphorylation of VEGFR2 and tyrosine phosphorylation of downstream substrates. GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation is a descendant of GO:0001934 (checked with OAK) and is the specific claim supported. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS TRANSFER Human donor evidence is sound; refined only in granularity. Proposed replacements: positive regulation of peptidyl-tyrosine phosphorylation Supporting Evidence: PMID:7929439 KDR was found to undergo ligand-induced autophosphorylation in intact cells |
| GO:0001935 endothelial cell proliferation | ISO GO_REF:0000121 | MODIFY | Summary: Endothelial cell proliferation: VEGF-A drives (positively regulates) it rather than proliferating itself. Reason: A secreted mitogen regulates the proliferation of target cells; the accepted GO:0001938 positive regulation of endothelial cell proliferation states this correctly. Lateral correction to the regulation term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Mouse phenotype is real; the term should be the regulation term. Proposed replacements: positive regulation of endothelial cell proliferation Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0001938 positive regulation of endothelial cell proliferation | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of endothelial cell proliferation. Reason: VEGF-A is an endothelial mitogen acting through VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0001938 positive regulation of endothelial cell proliferation | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of endothelial cell proliferation. Reason: VEGF-A is an endothelial mitogen acting through VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0001938 positive regulation of endothelial cell proliferation | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of endothelial cell proliferation. Reason: VEGF-A is an endothelial mitogen acting through VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0001938 positive regulation of endothelial cell proliferation | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of endothelial cell proliferation. Reason: VEGF-A is an endothelial mitogen acting through VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0001938 positive regulation of endothelial cell proliferation | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of endothelial cell proliferation. Reason: VEGF-A is an endothelial mitogen acting through VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0001938 positive regulation of endothelial cell proliferation | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of endothelial cell proliferation. Reason: VEGF-A is an endothelial mitogen acting through VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0001944 vasculature development | ISO GO_REF:0000121 | MODIFY | Summary: Vasculature development: true but general; refined to angiogenesis and vasculogenesis. Reason: GO:0001525 angiogenesis is part_of/is_a descendant of blood vessel development, as is vasculogenesis (GO:0001570) (checked with OAK). VEGF-A is required for both; the general phenotype-derived term is refined to these two processes. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Mouse knockout phenotype supports the claim; only granularity is refined. Proposed replacements: angiogenesis vasculogenesis Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0001946 lymphangiogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lymphangiogenesis (VEGF-A contributes; VEGF-C is the main lymphangiogenic factor). Reason: Lymphangiogenesis (VEGF-A contributes; VEGF-C is the main lymphangiogenic factor). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0001968 fibronectin binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Fibronectin binding contributes to matrix storage of VEGF-A. Reason: VEGF165 and VEGF121 bind fibronectin, which is enhanced at acidic pH (human source); this supports matrix storage and release. Non-core. Supporting Evidence: PMID:14570917 Here we report that VEGF(165) and VEGF(121) binding to fibronectin also increased at acidic pH |
| GO:0001974 blood vessel remodeling | IMP PMID:16203926 Vascular endothelial growth factor is required for coronary ... | KEEP AS NON CORE | Summary: Blood vessel remodeling: VEGF required for coronary collateral growth in rat. Reason: Rat IMP (anti-VEGF prevented collateral anastomosis formation). Arteriogenic remodeling is a context of VEGF-driven vessel growth; non-core. Supporting Evidence: PMID:16203926 X-ray micro-CT analysis revealed a 3-fold increase (versus sham group) in the number of arterial-arterial anastomoses per heart after RI, which was prevented by treatment with anti-VEGF. |
| GO:0002040 sprouting angiogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: Sprouting angiogenesis. Reason: VEGF-A gradients drive endothelial tip-cell sprouting via VEGFR2 and NRP1; conserved mammalian core process. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:0002040 sprouting angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Sprouting angiogenesis. Reason: VEGF-A gradients drive endothelial tip-cell sprouting via VEGFR2 and NRP1; conserved mammalian core process. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:0002042 cell migration involved in sprouting angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Cell migration involved in sprouting angiogenesis. Reason: VEGF-A is the chemotactic cue for migrating endothelial cells during sprouting. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:0002052 positive regulation of neuroblast proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of neuroblast proliferation (neurogenic effect via VEGFR2). Reason: Positive regulation of neuroblast proliferation (neurogenic effect via VEGFR2). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. |
| GO:0002053 positive regulation of mesenchymal cell proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of mesenchymal cell proliferation. Reason: Positive regulation of mesenchymal cell proliferation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0002092 positive regulation of receptor internalization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of receptor internalization (ligand-induced VEGFR2 endocytosis). Reason: Positive regulation of receptor internalization (ligand-induced VEGFR2 endocytosis). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:7929439 KDR was found to undergo ligand-induced autophosphorylation in intact cells |
| GO:0002575 basophil chemotaxis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Basophil chemotaxis (VEGF-A is chemotactic for human basophils). Reason: Basophil chemotaxis (VEGF-A is chemotactic for human basophils). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. |
| GO:0003007 heart morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Heart morphogenesis (mouse developmental phenotype). Reason: Heart morphogenesis (mouse developmental phenotype). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0003151 outflow tract morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Outflow tract morphogenesis (mouse isoform-specific developmental phenotype). Reason: Outflow tract morphogenesis (mouse isoform-specific developmental phenotype). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0003169 coronary vein morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Coronary vein morphogenesis (mouse isoform-specific developmental phenotype). Reason: Coronary vein morphogenesis (mouse isoform-specific developmental phenotype). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0005102 signaling receptor binding | ISO GO_REF:0000121 | MODIFY | Summary: Signaling receptor binding is correct but uninformative; the specific receptors are VEGFRs. Reason: GO:0005172 VEGF receptor binding is_a GO:0005102 signaling receptor binding (checked with OAK) and is accepted for this gene. The row is refined to the specific receptor family VEGF-A binds. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Mouse donor annotation is sound; refined only in granularity. PR:Q00731-2 · mouse Vegfa isoform SUPPORTS TRANSFER Mouse donor annotation is sound; refined only in granularity. Proposed replacements: vascular endothelial growth factor receptor binding Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. |
| GO:0005125 cytokine activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cytokine activity: VEGF-A has cytokine-like effects on immune cells. Reason: VEGF-A acts on monocytes, T cells and basophils (e.g. Th1 polarisation in rat T cells), so a cytokine-activity descriptor is defensible, but the primary activity is endothelial growth factor; non-core. Supporting Evidence: PMID:15034080 VEGF augmented IFN-gamma and inhibited IL-10 secretion by T cells responding to mitogen or Ag; thus, VEGF can enhance a Th1 phenotype. PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. |
| GO:0005161 platelet-derived growth factor receptor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: PDGF receptor binding: VEGF-A can bind and activate PDGFRalpha/beta on mesenchymal cells. Reason: Human MSC work shows VEGF-A binds PDGFRalpha and PDGFRbeta and induces their phosphorylation in the absence of VEGFRs. A real but secondary receptor interaction, transferred from human; non-core. Supporting Evidence: PMID:17470632 VEGF-A binds to both PDGFRalpha and PDGFRbeta and induces tyrosine phosphorylation PMID:17470632 VEGF-A can stimulate platelet-derived growth factor receptors (PDGFRs), thereby regulating MSC migration and proliferation |
| GO:0005172 vascular endothelial growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: VEGF receptor binding is the defining ligand-receptor interaction of VEGF-A. Reason: VEGF-A binds both VEGFR1/FLT1 and VEGFR2/KDR with high affinity (receptor expression cloning and binding analyses). Core function, conserved in rat. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. PMID:1417831 Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. PMID:1312256 These findings show that flt encodes a receptor for VEGF-VPF. |
| GO:0005172 vascular endothelial growth factor receptor binding | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF receptor binding is the defining ligand-receptor interaction of VEGF-A. Reason: VEGF-A binds both VEGFR1/FLT1 and VEGFR2/KDR with high affinity (receptor expression cloning and binding analyses). Core function, conserved in rat. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. PMID:1417831 Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. PMID:1312256 These findings show that flt encodes a receptor for VEGF-VPF. |
| GO:0005172 vascular endothelial growth factor receptor binding | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF receptor binding is the defining ligand-receptor interaction of VEGF-A. Reason: VEGF-A binds both VEGFR1/FLT1 and VEGFR2/KDR with high affinity (receptor expression cloning and binding analyses). Core function, conserved in rat. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. PMID:1417831 Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. PMID:1312256 These findings show that flt encodes a receptor for VEGF-VPF. |
| GO:0005172 vascular endothelial growth factor receptor binding | TAS PMID:12181492 Vascular endothelial growth factor (VEGF) stimulates neuroge... | ACCEPT | Summary: VEGF receptor binding is the defining ligand-receptor interaction of VEGF-A. Reason: VEGF-A binds both VEGFR1/FLT1 and VEGFR2/KDR with high affinity (receptor expression cloning and binding analyses). Core function, conserved in rat. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. PMID:1417831 Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. PMID:1312256 These findings show that flt encodes a receptor for VEGF-VPF. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Extracellular region: VEGF-A is a secreted growth factor. Reason: VEGF-A carries a cleaved signal peptide and is secreted; rat studies detect it in conditioned media of activated T cells, hypoxic cardiomyocytes and cardiomyocyte/Stro-1 cultures, and in growth-plate matrix vesicles. Core location. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. PMID:15034080 Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia PMID:12881220 Analysis of proteins secreted in HMCM showed increased levels of VEGF PMID:20097747 The HBR treatment enhanced the secretion of VEGF and HGF in the culture medium from both RCm and Stro-1 cells. |
| GO:0005576 extracellular region | IDA PMID:15034080 Angiogenesis-inflammation cross-talk: vascular endothelial g... | ACCEPT | Summary: Extracellular region: VEGF-A is a secreted growth factor. Reason: VEGF-A carries a cleaved signal peptide and is secreted; rat studies detect it in conditioned media of activated T cells, hypoxic cardiomyocytes and cardiomyocyte/Stro-1 cultures, and in growth-plate matrix vesicles. Core location. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. PMID:15034080 Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia PMID:12881220 Analysis of proteins secreted in HMCM showed increased levels of VEGF PMID:20097747 The HBR treatment enhanced the secretion of VEGF and HGF in the culture medium from both RCm and Stro-1 cells. |
| GO:0005576 extracellular region | IDA PMID:18758911 Matrix vesicles are carriers of bone morphogenetic proteins ... | ACCEPT | Summary: Extracellular region: VEGF-A is a secreted growth factor. Reason: VEGF-A carries a cleaved signal peptide and is secreted; rat studies detect it in conditioned media of activated T cells, hypoxic cardiomyocytes and cardiomyocyte/Stro-1 cultures, and in growth-plate matrix vesicles. Core location. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. PMID:15034080 Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia PMID:12881220 Analysis of proteins secreted in HMCM showed increased levels of VEGF PMID:20097747 The HBR treatment enhanced the secretion of VEGF and HGF in the culture medium from both RCm and Stro-1 cells. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Extracellular region: VEGF-A is a secreted growth factor. Reason: VEGF-A carries a cleaved signal peptide and is secreted; rat studies detect it in conditioned media of activated T cells, hypoxic cardiomyocytes and cardiomyocyte/Stro-1 cultures, and in growth-plate matrix vesicles. Core location. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. PMID:15034080 Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia PMID:12881220 Analysis of proteins secreted in HMCM showed increased levels of VEGF PMID:20097747 The HBR treatment enhanced the secretion of VEGF and HGF in the culture medium from both RCm and Stro-1 cells. |
| GO:0005576 extracellular region | ISO GO_REF:0000121 | ACCEPT | Summary: Extracellular region: VEGF-A is a secreted growth factor. Reason: VEGF-A carries a cleaved signal peptide and is secreted; rat studies detect it in conditioned media of activated T cells, hypoxic cardiomyocytes and cardiomyocyte/Stro-1 cultures, and in growth-plate matrix vesicles. Core location. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. PMID:15034080 Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia PMID:12881220 Analysis of proteins secreted in HMCM showed increased levels of VEGF PMID:20097747 The HBR treatment enhanced the secretion of VEGF and HGF in the culture medium from both RCm and Stro-1 cells. |
| GO:0005576 extracellular region | ISO GO_REF:0000121 | ACCEPT | Summary: Extracellular region: VEGF-A is a secreted growth factor. Reason: VEGF-A carries a cleaved signal peptide and is secreted; rat studies detect it in conditioned media of activated T cells, hypoxic cardiomyocytes and cardiomyocyte/Stro-1 cultures, and in growth-plate matrix vesicles. Core location. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. PMID:15034080 Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia PMID:12881220 Analysis of proteins secreted in HMCM showed increased levels of VEGF PMID:20097747 The HBR treatment enhanced the secretion of VEGF and HGF in the culture medium from both RCm and Stro-1 cells. |
| GO:0005576 extracellular region | ISO GO_REF:0000121 | ACCEPT | Summary: Extracellular region: VEGF-A is a secreted growth factor. Reason: VEGF-A carries a cleaved signal peptide and is secreted; rat studies detect it in conditioned media of activated T cells, hypoxic cardiomyocytes and cardiomyocyte/Stro-1 cultures, and in growth-plate matrix vesicles. Core location. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. PMID:15034080 Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia PMID:12881220 Analysis of proteins secreted in HMCM showed increased levels of VEGF PMID:20097747 The HBR treatment enhanced the secretion of VEGF and HGF in the culture medium from both RCm and Stro-1 cells. |
| GO:0005576 extracellular region | ISO GO_REF:0000121 | ACCEPT | Summary: Extracellular region: VEGF-A is a secreted growth factor. Reason: VEGF-A carries a cleaved signal peptide and is secreted; rat studies detect it in conditioned media of activated T cells, hypoxic cardiomyocytes and cardiomyocyte/Stro-1 cultures, and in growth-plate matrix vesicles. Core location. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. PMID:15034080 Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia PMID:12881220 Analysis of proteins secreted in HMCM showed increased levels of VEGF PMID:20097747 The HBR treatment enhanced the secretion of VEGF and HGF in the culture medium from both RCm and Stro-1 cells. |
| GO:0005576 extracellular region | ISO GO_REF:0000121 | ACCEPT | Summary: Extracellular region: VEGF-A is a secreted growth factor. Reason: VEGF-A carries a cleaved signal peptide and is secreted; rat studies detect it in conditioned media of activated T cells, hypoxic cardiomyocytes and cardiomyocyte/Stro-1 cultures, and in growth-plate matrix vesicles. Core location. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. PMID:15034080 Here we show that VEGF is secreted by T cells on stimulation by specific Ag or by IL-2 and by hypoxia PMID:12881220 Analysis of proteins secreted in HMCM showed increased levels of VEGF PMID:20097747 The HBR treatment enhanced the secretion of VEGF and HGF in the culture medium from both RCm and Stro-1 cells. |
| GO:0005604 basement membrane | IDA PMID:11940521 VEGF-induced mobilization of caveolae and increase in permea... | KEEP AS NON CORE | Summary: Basement membrane: VEGF-A deposited in the glomerular basement membrane. Reason: Rat immunoelectron microscopy places VEGF at podocytes and in the glomerular basement membrane, consistent with heparin/ECM retention of long isoforms. Correct, non-core extracellular sub-location. Supporting Evidence: PMID:11940521 Immunoelectron microscopy of glomeruli confirmed VEGF localization to podocytes and in the basement membrane. file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Nucleus: reported for the N-terminal L-VEGF-derived N-VEGF fragment in human. Reason: The human source localises the N-VEGF product of CUG-initiated L-VEGF to the nucleus under hypoxia. P16612 does not represent the L-VEGF extension, so this location concerns a non-canonical product; transfer is plausible given conserved 5' sequence but unverified in rat. Non-core. Supporting Evidence: file:human/VEGFA/VEGFA-uniprot.txt Cytoplasmic in normoxic conditions and localizes to the nucleus under hypoxic conditions. |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Nucleus: reported for the N-terminal L-VEGF-derived N-VEGF fragment in human. Reason: The human source localises the N-VEGF product of CUG-initiated L-VEGF to the nucleus under hypoxia. P16612 does not represent the L-VEGF extension, so this location concerns a non-canonical product; transfer is plausible given conserved 5' sequence but unverified in rat. Non-core. Supporting Evidence: file:human/VEGFA/VEGFA-uniprot.txt Cytoplasmic in normoxic conditions and localizes to the nucleus under hypoxic conditions. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cytoplasm: N-VEGF (from L-VEGF) is cytoplasmic in normoxia in human. Reason: Same basis as the nucleus row: human N-VEGF is cytoplasmic in normoxia. Secreted VEGF-A itself is extracellular. Non-core. Supporting Evidence: file:human/VEGFA/VEGFA-uniprot.txt Cytoplasmic in normoxic conditions and localizes to the nucleus under hypoxic conditions. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cytoplasm: N-VEGF (from L-VEGF) is cytoplasmic in normoxia in human. Reason: Same basis as the nucleus row: human N-VEGF is cytoplasmic in normoxia. Secreted VEGF-A itself is extracellular. Non-core. Supporting Evidence: file:human/VEGFA/VEGFA-uniprot.txt Cytoplasmic in normoxic conditions and localizes to the nucleus under hypoxic conditions. |
| GO:0005783 endoplasmic reticulum | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Endoplasmic reticulum: secretory-pathway location of VEGF-A, shown for human L-VEGF189. Reason: Root organelle term; checked the source: human UniProt records ER (and Golgi) localisation for isoform L-VEGF189 (ECO:0000269|PubMed:11731620). As a signal-peptide-bearing secreted protein, VEGF-A transits the ER, so the organelle claim holds; it is not where VEGF-A acts. Non-core. Supporting Evidence: file:human/VEGFA/VEGFA-uniprot.txt Endoplasmic reticulum {ECO:0000269|PubMed:11731620}. Golgi apparatus file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. |
| GO:0005794 Golgi apparatus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Golgi apparatus: secretory-pathway location shown for human L-VEGF189. Reason: Root organelle term; source checked as for the ER row (human L-VEGF189 in Golgi, ECO:0000269|PubMed:11731620). The organelle claim holds as a transit compartment for the secreted glycoprotein. Non-core. Supporting Evidence: file:human/VEGFA/VEGFA-uniprot.txt Endoplasmic reticulum {ECO:0000269|PubMed:11731620}. Golgi apparatus file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. |
| GO:0005912 adherens junction | ISO GO_REF:0000121 | UNDECIDED | Summary: Adherens junction location transferred from a human IDA that could not be verified. Reason: The human source (PMID:26598555, ARUK-UCL IDA) is a study of BMP-induced permeability and VE-cadherin; its abstract does not describe VEGF-A at adherens junctions, and full text was not available. VEGF-A acts on adherens junctions (VE-cadherin phosphorylation) without itself being a junctional component, so the location is uncertain. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P15692 · human VEGFA UNRESOLVED Human donor IDA (PMID:26598555) abstract does not show VEGF-A at adherens junctions; full text unavailable. |
| GO:0006357 regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of transcription by RNA polymerase II: distal output of VEGF signalling. Reason: VEGF-A is a secreted ligand with no transcription-regulatory activity; changes in target-gene transcription are distal consequences of receptor signalling and are better captured by the VEGFR signalling terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS SOURCE BUT NOT TARGET Donor evidence shows downstream target-gene induction, not transcription regulation by VEGF-A itself. UniProtKB:P15692-4 · human VEGFA isoform VEGF121 SUPPORTS SOURCE BUT NOT TARGET Donor evidence shows downstream target-gene induction, not transcription regulation by VEGF-A itself. Supporting Evidence: file:rat/Vegfa/Vegfa-deep-research-manual.md Transcription, mRNA-stability and gene-expression rows reflect distal signalling outputs, not activities of VEGF-A itself. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | ISO GO_REF:0000121 | REMOVE | Summary: PLC-activating G protein-coupled receptor signaling pathway: wrong pathway; VEGF receptors are receptor tyrosine kinases. Reason: VEGF-A signals through the receptor tyrosine kinases VEGFR1/2, which activate PLCgamma directly; no GPCR is involved. The human donor (PMID:18059339) reports VEGFR2/KDR and PKC-mediated signalling, which is VEGFR2 signalling, not GPCR signalling. The ISO row propagates a mis-termed donor annotation and is contradicted by the receptor biology. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P15692 · human VEGFA SOURCE BAD Human BHF-UCL IDA from PMID:18059339 used a GPCR pathway term for VEGFR2 (RTK)/PKC signalling. Supporting Evidence: PMID:18059339 VEGF induced a rapid increase in Egr-dependent transcriptional activation mediated via its major signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway PMID:1417831 Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. |
| GO:0007399 nervous system development | IDA PMID:12181492 Vascular endothelial growth factor (VEGF) stimulates neuroge... | MODIFY | Summary: Nervous system development: VEGF-A stimulates neurogenesis. Reason: Rat studies (full text PMID:12181492; PMID:15258583 abstract) show VEGF increases BrdU-labelled neuronal precursors in vitro and in adult rat SVZ/SGZ, and hippocampal VEGF gene transfer doubles neurogenesis. GO:0022008 neurogenesis is part_of GO:0007399 (checked with OAK) and is the specific process supported. Proposed replacements: neurogenesis Supporting Evidence: PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. PMID:15258583 Hippocampal gene transfer of VEGF in adult rats resulted in approximately 2 times more neurogenesis associated with improved cognition. |
| GO:0007399 nervous system development | NAS PMID:15258583 VEGF links hippocampal activity with neurogenesis, learning ... | MODIFY | Summary: Nervous system development: VEGF-A stimulates neurogenesis. Reason: Rat studies (full text PMID:12181492; PMID:15258583 abstract) show VEGF increases BrdU-labelled neuronal precursors in vitro and in adult rat SVZ/SGZ, and hippocampal VEGF gene transfer doubles neurogenesis. GO:0022008 neurogenesis is part_of GO:0007399 (checked with OAK) and is the specific process supported. Proposed replacements: neurogenesis Supporting Evidence: PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. PMID:15258583 Hippocampal gene transfer of VEGF in adult rats resulted in approximately 2 times more neurogenesis associated with improved cognition. |
| GO:0007498 mesoderm development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mesoderm development (mouse developmental phenotype). Reason: Mesoderm development (mouse developmental phenotype). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0007565 female pregnancy | IEP PMID:16959835 Glucocorticoids prevent the normal increase in placental vas... | KEEP AS NON CORE | Summary: Female pregnancy: placental VEGF rises during late pregnancy with labyrinth vascularisation. Reason: Expression evidence in rat placenta paralleling vascular development; peripheral context of the angiogenic function. Supporting Evidence: PMID:16959835 expression of VEGF was markedly up-regulated specifically in the rapidly growing labyrinth zone over the final third of normal pregnancy |
| GO:0007595 lactation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lactation (mammary vascular permeability; expression rises in lactation). Reason: Lactation (mammary vascular permeability; expression rises in lactation). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt May play a role in increasing vascular permeability during lactation |
| GO:0008083 growth factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Growth factor activity: VEGF-A is the prototypic endothelial growth factor. Reason: VEGF-A is a secreted homodimeric cystine-knot growth factor that stimulates proliferation, survival and migration of endothelial and other VEGFR-expressing cells; in rat cortical cultures it stimulates neural-precursor BrdU incorporation through VEGFR2. Core molecular function. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0008083 growth factor activity | IDA PMID:12181492 Vascular endothelial growth factor (VEGF) stimulates neuroge... | ACCEPT | Summary: Growth factor activity: VEGF-A is the prototypic endothelial growth factor. Reason: VEGF-A is a secreted homodimeric cystine-knot growth factor that stimulates proliferation, survival and migration of endothelial and other VEGFR-expressing cells; in rat cortical cultures it stimulates neural-precursor BrdU incorporation through VEGFR2. Core molecular function. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0008083 growth factor activity | IDA PMID:16160062 HMG CoA reductase inhibition modulates VEGF-induced endothel... | ACCEPT | Summary: Growth factor activity: VEGF-A is the prototypic endothelial growth factor. Reason: VEGF-A is a secreted homodimeric cystine-knot growth factor that stimulates proliferation, survival and migration of endothelial and other VEGFR-expressing cells; in rat cortical cultures it stimulates neural-precursor BrdU incorporation through VEGFR2. Core molecular function. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0008083 growth factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Growth factor activity: VEGF-A is the prototypic endothelial growth factor. Reason: VEGF-A is a secreted homodimeric cystine-knot growth factor that stimulates proliferation, survival and migration of endothelial and other VEGFR-expressing cells; in rat cortical cultures it stimulates neural-precursor BrdU incorporation through VEGFR2. Core molecular function. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0008083 growth factor activity | ISO GO_REF:0000121 | ACCEPT | Summary: Growth factor activity: VEGF-A is the prototypic endothelial growth factor. Reason: VEGF-A is a secreted homodimeric cystine-knot growth factor that stimulates proliferation, survival and migration of endothelial and other VEGFR-expressing cells; in rat cortical cultures it stimulates neural-precursor BrdU incorporation through VEGFR2. Core molecular function. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0008083 growth factor activity | ISO GO_REF:0000121 | ACCEPT | Summary: Growth factor activity: VEGF-A is the prototypic endothelial growth factor. Reason: VEGF-A is a secreted homodimeric cystine-knot growth factor that stimulates proliferation, survival and migration of endothelial and other VEGFR-expressing cells; in rat cortical cultures it stimulates neural-precursor BrdU incorporation through VEGFR2. Core molecular function. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0008201 heparin binding | IEA GO_REF:0000002 | ACCEPT | Summary: Heparin binding via the basic exon 6/7-encoded domains. Reason: Heparin and heparan sulfate binding by the basic C-terminal domains of VEGF-A164/188 determines matrix retention and bioavailability, and is a documented rat feature. Core property of the long isoforms. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix |
| GO:0008201 heparin binding | ISO GO_REF:0000121 | ACCEPT | Summary: Heparin binding via the basic exon 6/7-encoded domains. Reason: Heparin and heparan sulfate binding by the basic C-terminal domains of VEGF-A164/188 determines matrix retention and bioavailability, and is a documented rat feature. Core property of the long isoforms. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix |
| GO:0008201 heparin binding | ISO GO_REF:0000121 | ACCEPT | Summary: Heparin binding via the basic exon 6/7-encoded domains. Reason: Heparin and heparan sulfate binding by the basic C-terminal domains of VEGF-A164/188 determines matrix retention and bioavailability, and is a documented rat feature. Core property of the long isoforms. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix |
| GO:0008283 cell population proliferation | ISO GO_REF:0000121 | MODIFY | Summary: Cell population proliferation: VEGF-A positively regulates proliferation of target cells. Reason: Lateral correction to GO:0008284 positive regulation of cell population proliferation, which is accepted on rat IMP and other evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Mouse phenotype is real; the regulation term is the correct form for a mitogen. Proposed replacements: positive regulation of cell population proliferation Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:18614764 endogenous VEGF signaling during insult was essential for cell fate since VEGF inhibition appreciably augmented cell death and reduced proliferation. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:18614764 Astrocyte responses to injury: VEGF simultaneously modulates... | ACCEPT | Summary: Positive regulation of cell population proliferation. Reason: VEGF-A is a mitogen; rat astrocyte study shows VEGF inhibition reduced proliferation, and VEGF stimulates neural-precursor proliferation. Core output of growth factor activity. Supporting Evidence: PMID:18614764 endogenous VEGF signaling during insult was essential for cell fate since VEGF inhibition appreciably augmented cell death and reduced proliferation. PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0008284 positive regulation of cell population proliferation | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of cell population proliferation. Reason: VEGF-A is a mitogen; rat astrocyte study shows VEGF inhibition reduced proliferation, and VEGF stimulates neural-precursor proliferation. Core output of growth factor activity. Supporting Evidence: PMID:18614764 endogenous VEGF signaling during insult was essential for cell fate since VEGF inhibition appreciably augmented cell death and reduced proliferation. PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0008284 positive regulation of cell population proliferation | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of cell population proliferation. Reason: VEGF-A is a mitogen; rat astrocyte study shows VEGF inhibition reduced proliferation, and VEGF stimulates neural-precursor proliferation. Core output of growth factor activity. Supporting Evidence: PMID:18614764 endogenous VEGF signaling during insult was essential for cell fate since VEGF inhibition appreciably augmented cell death and reduced proliferation. PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0008284 positive regulation of cell population proliferation | TAS PMID:12181492 Vascular endothelial growth factor (VEGF) stimulates neuroge... | ACCEPT | Summary: Positive regulation of cell population proliferation. Reason: VEGF-A is a mitogen; rat astrocyte study shows VEGF inhibition reduced proliferation, and VEGF stimulates neural-precursor proliferation. Core output of growth factor activity. Supporting Evidence: PMID:18614764 endogenous VEGF signaling during insult was essential for cell fate since VEGF inhibition appreciably augmented cell death and reduced proliferation. PMID:12181492 VEGF (>10 ng/ml) stimulated 5-bromo-2′-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0008360 regulation of cell shape | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of cell shape (VEGF-induced cytoskeletal reorganisation). Reason: Regulation of cell shape (VEGF-induced cytoskeletal reorganisation). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0009967 positive regulation of signal transduction | IDA PMID:12483534 Coordinating Etk/Bmx activation and VEGF upregulation to pro... | TOO GENERAL | Summary: Positive regulation of signal transduction is entailed by the specific signalling terms carried. Reason: The rat IDA (VEGF stimulates Etk tyrosine phosphorylation in HUVECs) is real, but positive regulation of MAPK cascade, ERK1/2 cascade and PI3K/AKT signalling, all carried here, are descendants of GO:0009967 (checked with OAK). Supporting Evidence: PMID:12483534 exogenous VEGF treatment stimulates endogenous Etk tyrosine phosphorylation in HUVECs |
| GO:0009986 cell surface | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cell surface: cell-associated VEGF-A bound to heparan sulfate/receptors. Reason: Basic isoforms remain cell-associated after secretion through heparan sulfate binding, and VEGF-A binds surface VEGFRs/NRP1. Correct but peripheral to function. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. |
| GO:0010595 positive regulation of endothelial cell migration | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of endothelial cell migration. Reason: VEGF-A promotes endothelial migration via VEGFR2 and NRP1. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:0010595 positive regulation of endothelial cell migration | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of endothelial cell migration. Reason: VEGF-A promotes endothelial migration via VEGFR2 and NRP1. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:0010595 positive regulation of endothelial cell migration | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of endothelial cell migration. Reason: VEGF-A promotes endothelial migration via VEGFR2 and NRP1. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Positive regulation of gene expression: distal consequence of VEGF signalling. Reason: As for the transcription rows: target-gene induction is downstream of receptor signalling, not an activity of VEGF-A. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS SOURCE BUT NOT TARGET Donor evidence reflects downstream gene induction. UniProtKB:P15692-4 · human VEGFA isoform VEGF121 SUPPORTS SOURCE BUT NOT TARGET Donor evidence reflects downstream gene induction. Supporting Evidence: file:rat/Vegfa/Vegfa-deep-research-manual.md Transcription, mRNA-stability and gene-expression rows reflect distal signalling outputs, not activities of VEGF-A itself. |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Negative regulation of gene expression: distal consequence of VEGF signalling. Reason: As for the transcription rows: repression of target genes downstream of VEGF signalling (human sources include microRNA-related studies) is not an activity of VEGF-A. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS SOURCE BUT NOT TARGET Donor evidence reflects downstream expression changes. Supporting Evidence: file:rat/Vegfa/Vegfa-deep-research-manual.md Transcription, mRNA-stability and gene-expression rows reflect distal signalling outputs, not activities of VEGF-A itself. |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Negative regulation of gene expression: distal consequence of VEGF signalling. Reason: As for the transcription rows: repression of target genes downstream of VEGF signalling (human sources include microRNA-related studies) is not an activity of VEGF-A. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS SOURCE BUT NOT TARGET Donor evidence reflects downstream expression changes. Supporting Evidence: file:rat/Vegfa/Vegfa-deep-research-manual.md Transcription, mRNA-stability and gene-expression rows reflect distal signalling outputs, not activities of VEGF-A itself. |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Negative regulation of gene expression: distal consequence of VEGF signalling. Reason: As for the transcription rows: repression of target genes downstream of VEGF signalling (human sources include microRNA-related studies) is not an activity of VEGF-A. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS SOURCE BUT NOT TARGET Donor evidence reflects downstream expression changes. UniProtKB:P15692-4 · human VEGFA isoform VEGF121 SUPPORTS SOURCE BUT NOT TARGET Donor evidence reflects downstream expression changes. Supporting Evidence: file:rat/Vegfa/Vegfa-deep-research-manual.md Transcription, mRNA-stability and gene-expression rows reflect distal signalling outputs, not activities of VEGF-A itself. |
| GO:0010719 negative regulation of epithelial to mesenchymal transition | ISO GO_REF:0000121 | UNDECIDED | Summary: Negative regulation of epithelial to mesenchymal transition: transferred from mouse; source not inspected. Reason: No rat or cached donor evidence; the mouse source annotation could not be inspected. VEGF-A is not established as an EMT regulator in the reviewed literature. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: MGI:MGI:103178 · mouse Vegfa UNRESOLVED Mouse donor evidence not inspected. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Membrane: InterPro2GO mapping from the PDGF/VEGF domain; VEGF-A is a secreted soluble protein. Reason: VEGF-A has no transmembrane segment and is secreted; the IPR000072 PDGF/VEGF domain mapping to membrane is not informative for this soluble ligand. Its pericellular retention is captured by cell surface and extracellular matrix terms. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A120 is acidic and freely secreted. file:rat/Vegfa/Vegfa-uniprot.txt Belongs to the PDGF/VEGF growth factor family. |
| GO:0016477 cell migration | ISO GO_REF:0000121 | MODIFY | Summary: Cell migration: VEGF-A promotes migration of target cells. Reason: Lateral correction to GO:0030335 positive regulation of cell migration, accepted here; VEGF-A is the migratory cue, not the migrating entity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Mouse phenotype is real; refined to the regulation term. Proposed replacements: positive regulation of cell migration Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0019838 growth factor binding | IPI PMID:17881084 Heparin affin regulatory peptide/pleiotrophin negatively aff... | KEEP AS NON CORE | Summary: Growth factor binding: VEGF-A binds pleiotrophin (HARP) in rat C6 glioma cells. Reason: Rat C6 glioma study (IPI with RGD:3444 pleiotrophin) shows a direct interaction of HARP with VEGF that sequesters VEGF from VEGFR2. A regulatory interaction, not VEGF-A activity; non-core. Abstract-only; deferring to the curator on the IPI. Supporting Evidence: PMID:17881084 The above results seem to be due to a direct interaction between HARP and VEGF in the culture medium of C6 and PC-C6 cells |
| GO:0022408 negative regulation of cell-cell adhesion | ISO GO_REF:0000121 | MODIFY | Summary: Negative regulation of cell-cell adhesion: correct but more general than the cadherin-specific term the gene carries. Reason: GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin is_a GO:0022408 (checked with OAK) and is accepted for this gene; refine to it. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Mouse donor phenotype is sound; refined only in granularity. Proposed replacements: negative regulation of cell-cell adhesion mediated by cadherin Supporting Evidence: PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:0030141 secretory granule | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Secretory granule: VEGF-A stored in leukocyte secretory granules. Reason: Human basophils store VEGF-A in secretory granules and release it on activation (donor evidence for the ISO row). Cell-type-specific storage; non-core. Supporting Evidence: PMID:17082651 Peripheral blood and basophils in nasal polyps contain VEGF-A localized in secretory granules. |
| GO:0030224 monocyte differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Monocyte differentiation. Reason: Monocyte differentiation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0030225 macrophage differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Macrophage differentiation. Reason: Macrophage differentiation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0030297 transmembrane receptor protein tyrosine kinase activator activity | ISO GO_REF:0000121 | ACCEPT | Summary: Transmembrane RTK activator activity: VEGF-A activates the VEGFR receptor tyrosine kinases. Reason: VEGF-A binding induces dimerisation and autophosphorylation of the receptor tyrosine kinases VEGFR2/KDR and VEGFR1/FLT1. This is the most specific description of the activity VEGF-A performs on its receptors. Core. Supporting Evidence: PMID:7929439 KDR was found to undergo ligand-induced autophosphorylation in intact cells PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. |
| GO:0030324 lung development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Lung development (VEGF required for alveolarisation and lung vasculature). Reason: Lung development (VEGF required for alveolarisation and lung vasculature). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries |
| GO:0030324 lung development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lung development (VEGF required for alveolarisation and lung vasculature). Reason: Lung development (VEGF required for alveolarisation and lung vasculature). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries |
| GO:0030324 lung development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lung development (VEGF required for alveolarisation and lung vasculature). Reason: Lung development (VEGF required for alveolarisation and lung vasculature). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries |
| GO:0030335 positive regulation of cell migration | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of cell migration. Reason: VEGF-A promotes migration of endothelial cells and other VEGFR-expressing cells (rat C6 glioma, VSMC). Core output. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:14693680 Endogenous vascular endothelial growth factor-A (VEGF-A) was responsible for the mitogenic activity of MCP-1, because neutralizing anti-VEGF-A antibody inhibited cell proliferation in response to MCP-1. |
| GO:0030855 epithelial cell differentiation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Epithelial cell differentiation: indirect phenotype. Reason: Mouse phenotype-derived annotation; VEGF-A effects on epithelial differentiation (e.g. lung) are secondary to vascular development. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS SOURCE BUT NOT TARGET Mouse phenotype-derived; indirect. |
| GO:0031077 post-embryonic camera-type eye development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Post-embryonic camera-type eye development. Reason: Post-embryonic camera-type eye development. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0031290 retinal ganglion cell axon guidance | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Retinal ganglion cell axon guidance (NRP1-dependent VEGF-A164 guidance). Reason: Retinal ganglion cell axon guidance (NRP1-dependent VEGF-A164 guidance). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration |
| GO:0031290 retinal ganglion cell axon guidance | ISO NOT GO_REF:0000121 | KEEP AS NON CORE | Summary: NOT annotation, transferred from a mouse short-isoform result: Retinal ganglion cell axon guidance (NRP1-dependent VEGF-A164 guidance). Reason: This NOT row derives from mouse isoform PR:Q00731-3 (a short, non-NRP1-binding isoform) while the positive rows on the same term derive from PR:Q00731-2. Both can hold: NRP1-binding heparin-binding isoforms mediate this guidance response and the short isoform does not. The rat ISO row has lost the isoform context. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration |
| GO:0031334 positive regulation of protein-containing complex assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of protein-containing complex assembly (receptor dimerisation / NRP1-VEGFR2 complex). Reason: Positive regulation of protein-containing complex assembly (receptor dimerisation / NRP1-VEGFR2 complex). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:7929439 KDR was found to undergo ligand-induced autophosphorylation in intact cells |
| GO:0031982 vesicle | IDA PMID:18758911 Matrix vesicles are carriers of bone morphogenetic proteins ... | MODIFY | Summary: Vesicle: VEGF-A detected in growth-plate matrix vesicles, which are extracellular vesicles. Reason: Matrix vesicles isolated from rat growth plate are extracellular vesicles; GO:1903561 extracellular vesicle is_a GO:0031982 vesicle (checked with OAK). The general vesicle term is refined to the extracellular vesicle the assay actually isolated. Proposed replacements: extracellular vesicle Supporting Evidence: PMID:18758911 BMP-1 through-7, VEGF, BSP, ON, OPN, and OC were all detected by Western blot analyses. PMID:18758911 MVs were isolated from collagenase-digested rachitic rat tibial and femoral growth plates. |
| GO:0032355 response to estradiol | IEP PMID:8344219 Vascular endothelial growth factor/vascular permeability fac... | KEEP AS NON CORE | Summary: Response to estradiol: rapid estrogen induction of uterine VEGF. Reason: Rat uterus IEP; VEGF mediates estrogen-induced uterine permeability. Peripheral context. Supporting Evidence: PMID:8344219 Treatment with both estradiol (E2) and estriol (E3) rapidly induced an increase in the level of the two smaller transcripts. |
| GO:0032570 response to progesterone | IEP PMID:8344219 Vascular endothelial growth factor/vascular permeability fac... | KEEP AS NON CORE | Summary: Response to progesterone: progesterone induces uterine VEGF164/120. Reason: Rat uterus IEP; peripheral. Supporting Evidence: PMID:8344219 Progesterone also stimulated the expression (at 6 h) of VEG/PF164 and VEG/PF120, but not that of VEG/PF188. |
| GO:0033189 response to vitamin A | IEP PMID:23106861 The wound healing effects of vitamin A eye drops after a cor... | MARK AS OVER ANNOTATED | Summary: Response to vitamin A: lower VEGF-A after retinyl palmitate in alkali-burned cornea. Reason: VEGF-A was lower in treated corneas that healed better; the change tracks the altered wound state and neovascularisation, not a response of Vegfa to vitamin A per se. Supporting Evidence: PMID:23106861 VEGF-A, MMP 9 and TGF-β proteins were higher in the control group |
| GO:0035148 tube formation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Tube formation (endothelial tubulogenesis readout). Reason: Tube formation (endothelial tubulogenesis readout). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0035148 tube formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Tube formation (endothelial tubulogenesis readout). Reason: Tube formation (endothelial tubulogenesis readout). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0035767 endothelial cell chemotaxis | ISO GO_REF:0000121 | ACCEPT | Summary: Endothelial cell chemotaxis. Reason: VEGF-A is the chemoattractant that drives endothelial chemotaxis. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | ISO GO_REF:0000121 | TOO GENERAL | Summary: Cellular response to VEGF stimulus is an ancestor of the VEGF signaling pathway terms accepted here. Reason: GO:0038084 VEGF signaling pathway is_a GO:0035924 cellular response to VEGF stimulus (checked with OAK). VEGF-A is the ligand initiating that signalling, which is captured by the accepted pathway terms; the response term adds nothing and would be read as VEGF-A being a responder to itself. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION GRANULARITY MISMATCH Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Donor annotation carries the same scoping issue; transfer itself is faithful. Supporting Evidence: PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | ISO GO_REF:0000121 | TOO GENERAL | Summary: Cellular response to VEGF stimulus is an ancestor of the VEGF signaling pathway terms accepted here. Reason: GO:0038084 VEGF signaling pathway is_a GO:0035924 cellular response to VEGF stimulus (checked with OAK). VEGF-A is the ligand initiating that signalling, which is captured by the accepted pathway terms; the response term adds nothing and would be read as VEGF-A being a responder to itself. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION GRANULARITY MISMATCH Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS TRANSFER Donor annotation carries the same scoping issue; transfer itself is faithful. Supporting Evidence: PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. |
| GO:0036303 lymph vessel morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lymph vessel morphogenesis (secondary contribution, consistent with lymphangiogenesis). Reason: Lymph vessel morphogenesis (secondary contribution, consistent with lymphangiogenesis). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGFR-2 signaling pathway. Reason: VEGFR2 is the main transducer of VEGF-A signals. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. |
| GO:0038033 positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of endothelial cell chemotaxis by VEGF-activated VEGFR signaling. Reason: Precisely describes VEGF-A as endothelial chemoattractant through VEGFR2. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0038084 vascular endothelial growth factor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: VEGF signaling pathway: VEGF-A is the pathway ligand. Reason: Core; VEGF-A initiates the pathway through VEGFR binding. Supporting Evidence: PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0038084 vascular endothelial growth factor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF signaling pathway: VEGF-A is the pathway ligand. Reason: Core; VEGF-A initiates the pathway through VEGFR binding. Supporting Evidence: PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0038084 vascular endothelial growth factor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF signaling pathway: VEGF-A is the pathway ligand. Reason: Core; VEGF-A initiates the pathway through VEGFR binding. Supporting Evidence: PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0038091 positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of cell proliferation by VEGF-activated PDGFR signaling (mesenchymal cells). Reason: Positive regulation of cell proliferation by VEGF-activated PDGFR signaling (mesenchymal cells). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:17470632 VEGF-A can stimulate platelet-derived growth factor receptors (PDGFRs), thereby regulating MSC migration and proliferation |
| GO:0038190 VEGF-activated neuropilin signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-activated neuropilin signaling pathway. Reason: NRP1-binding VEGF-A isoforms initiate NRP1 signalling for endothelial migration and axon guidance. Core co-receptor pathway. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:0038190 VEGF-activated neuropilin signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-activated neuropilin signaling pathway. Reason: NRP1-binding VEGF-A isoforms initiate NRP1 signalling for endothelial migration and axon guidance. Core co-receptor pathway. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:0038191 neuropilin binding | ISO GO_REF:0000121 | ACCEPT | Summary: Neuropilin binding: heparin-binding VEGF-A isoforms bind NRP1 as a co-receptor. Reason: NRP1 binds VEGF-A (exon 7/8-containing isoforms) and acts as a VEGFR2 co-receptor needed for endothelial migration and NRP1-dependent axon guidance. Core co-receptor interaction. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration PMID:21653826 In endothelial cells, neuropilin-1 (NRP1) binds vascular endothelial growth factor (VEGF)-A and is thought to act as a coreceptor for kinase insert domain-containing receptor (KDR) |
| GO:0040008 regulation of growth | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of growth: vague organismal-growth phenotype from mouse. Reason: Derives from growth phenotypes of Vegfa mutant mice, which are secondary to vascular defects. The term does not describe a process VEGF-A executes; its growth-factor role is captured by specific proliferation and angiogenesis terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS SOURCE BUT NOT TARGET Mouse phenotype is real but indirect. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0042056 chemoattractant activity | IBA GO_REF:0000033 | ACCEPT | Summary: Chemoattractant activity for endothelial cells and VEGFR-expressing leukocytes. Reason: VEGF-A gradients direct endothelial tip-cell migration and chemotaxis via VEGFR2, and VEGF-A is chemotactic for monocytes and basophils. Core activity underlying sprouting angiogenesis. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0042056 chemoattractant activity | ISO GO_REF:0000121 | ACCEPT | Summary: Chemoattractant activity for endothelial cells and VEGFR-expressing leukocytes. Reason: VEGF-A gradients direct endothelial tip-cell migration and chemotaxis via VEGFR2, and VEGF-A is chemotactic for monocytes and basophils. Core activity underlying sprouting angiogenesis. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0042056 chemoattractant activity | ISO GO_REF:0000121 | ACCEPT | Summary: Chemoattractant activity for endothelial cells and VEGFR-expressing leukocytes. Reason: VEGF-A gradients direct endothelial tip-cell migration and chemotaxis via VEGFR2, and VEGF-A is chemotactic for monocytes and basophils. Core activity underlying sprouting angiogenesis. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0042056 chemoattractant activity | ISO GO_REF:0000121 | ACCEPT | Summary: Chemoattractant activity for endothelial cells and VEGFR-expressing leukocytes. Reason: VEGF-A gradients direct endothelial tip-cell migration and chemotaxis via VEGFR2, and VEGF-A is chemotactic for monocytes and basophils. Core activity underlying sprouting angiogenesis. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0042088 T-helper 1 type immune response | IDA PMID:15034080 Angiogenesis-inflammation cross-talk: vascular endothelial g... | KEEP AS NON CORE | Summary: T-helper 1 type immune response: VEGF enhances Th1 polarisation of rat T cells. Reason: Rat T-cell study (abstract): VEGF augmented IFN-gamma and inhibited IL-10. Immune side-role; non-core. Supporting Evidence: PMID:15034080 VEGF augmented IFN-gamma and inhibited IL-10 secretion by T cells responding to mitogen or Ag; thus, VEGF can enhance a Th1 phenotype. |
| GO:0042311 vasodilation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Vasodilation (VEGF-induced NO-dependent vasodilation). Reason: Vasodilation (VEGF-induced NO-dependent vasodilation). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0042462 eye photoreceptor cell development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Eye photoreceptor cell development. Reason: Eye photoreceptor cell development. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0042802 identical protein binding | IPI PMID:2320579 Amino acid and cDNA sequences of a vascular endothelial cell... | KEEP AS NON CORE | Summary: Identical protein binding reflects the disulfide-linked VEGF-A homodimer. Reason: The active growth factor is an antiparallel disulfide-linked homodimer, first shown for the rat glioma protein. Structural, non-core MF. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Homodimer; disulfide-linked (PubMed:7706320). PMID:2320579 The GD-VEGF homodimeric subunit is homologous to the platelet-derived growth factor A and B chains PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Identical protein binding reflects the disulfide-linked VEGF-A homodimer. Reason: The active growth factor is an antiparallel disulfide-linked homodimer, first shown for the rat glioma protein. Structural, non-core MF. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Homodimer; disulfide-linked (PubMed:7706320). PMID:2320579 The GD-VEGF homodimeric subunit is homologous to the platelet-derived growth factor A and B chains PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Identical protein binding reflects the disulfide-linked VEGF-A homodimer. Reason: The active growth factor is an antiparallel disulfide-linked homodimer, first shown for the rat glioma protein. Structural, non-core MF. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Homodimer; disulfide-linked (PubMed:7706320). PMID:2320579 The GD-VEGF homodimeric subunit is homologous to the platelet-derived growth factor A and B chains PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process (endothelial and neuronal survival). Reason: Negative regulation of apoptotic process (endothelial and neuronal survival). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:17591953 VEGF-A exposure resulted in a dose-dependent reduction in retinal neuron apoptosis. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process (endothelial and neuronal survival). Reason: Negative regulation of apoptotic process (endothelial and neuronal survival). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:17591953 VEGF-A exposure resulted in a dose-dependent reduction in retinal neuron apoptosis. |
| GO:0043069 negative regulation of programmed cell death | IMP PMID:18614764 Astrocyte responses to injury: VEGF simultaneously modulates... | KEEP AS NON CORE | Summary: Negative regulation of programmed cell death: endogenous VEGF protects rat astrocytes. Reason: Rat IMP; survival effect of the growth factor; non-core. Supporting Evidence: PMID:18614764 endogenous VEGF signaling during insult was essential for cell fate since VEGF inhibition appreciably augmented cell death and reduced proliferation. |
| GO:0043117 positive regulation of vascular permeability | IEA GO_REF:0000117 | ACCEPT | Summary: Positive regulation of vascular permeability (VEGF = vascular permeability factor). Reason: Rat in vivo: soluble VEGFR2 prevented ischaemia-reperfusion-induced lung vascular permeability; VEGF increases glomerular endothelial permeability. Core. Supporting Evidence: PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. PMID:16160062 Our findings indicate that VEGF stimulation elicits a robust increase in GEnC permeability. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0043117 positive regulation of vascular permeability | IMP PMID:16793871 Activation of the stress protein response prevents the devel... | ACCEPT | Summary: Positive regulation of vascular permeability (VEGF = vascular permeability factor). Reason: Rat in vivo: soluble VEGFR2 prevented ischaemia-reperfusion-induced lung vascular permeability; VEGF increases glomerular endothelial permeability. Core. Supporting Evidence: PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. PMID:16160062 Our findings indicate that VEGF stimulation elicits a robust increase in GEnC permeability. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0043117 positive regulation of vascular permeability | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of vascular permeability (VEGF = vascular permeability factor). Reason: Rat in vivo: soluble VEGFR2 prevented ischaemia-reperfusion-induced lung vascular permeability; VEGF increases glomerular endothelial permeability. Core. Supporting Evidence: PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. PMID:16160062 Our findings indicate that VEGF stimulation elicits a robust increase in GEnC permeability. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0043117 positive regulation of vascular permeability | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of vascular permeability (VEGF = vascular permeability factor). Reason: Rat in vivo: soluble VEGFR2 prevented ischaemia-reperfusion-induced lung vascular permeability; VEGF increases glomerular endothelial permeability. Core. Supporting Evidence: PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. PMID:16160062 Our findings indicate that VEGF stimulation elicits a robust increase in GEnC permeability. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0043117 positive regulation of vascular permeability | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of vascular permeability (VEGF = vascular permeability factor). Reason: Rat in vivo: soluble VEGFR2 prevented ischaemia-reperfusion-induced lung vascular permeability; VEGF increases glomerular endothelial permeability. Core. Supporting Evidence: PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. PMID:16160062 Our findings indicate that VEGF stimulation elicits a robust increase in GEnC permeability. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0043129 surfactant homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Surfactant homeostasis (mouse fetal lung maturation phenotype). Reason: Surfactant homeostasis (mouse fetal lung maturation phenotype). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0043183 vascular endothelial growth factor receptor 1 binding | ISO GO_REF:0000121 | ACCEPT | Summary: VEGFR1/FLT1 binding. Reason: VEGF-A binds FLT1 with high affinity (Kd ~16 pM); FLT1 acts as a high-affinity, weakly signalling receptor. Core binding partner. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:1312256 These findings show that flt encodes a receptor for VEGF-VPF. PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. |
| GO:0043183 vascular endothelial growth factor receptor 1 binding | ISO GO_REF:0000121 | ACCEPT | Summary: VEGFR1/FLT1 binding. Reason: VEGF-A binds FLT1 with high affinity (Kd ~16 pM); FLT1 acts as a high-affinity, weakly signalling receptor. Core binding partner. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:1312256 These findings show that flt encodes a receptor for VEGF-VPF. PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | IEA GO_REF:0000117 | ACCEPT | Summary: VEGFR2/KDR binding; VEGFR2 is the main signal-transducing receptor. Reason: KDR is a high-affinity VEGF receptor whose ligand-induced autophosphorylation drives chemotaxis and mitogenesis; rat studies show VEGF effects blocked by VEGFR2 kinase inhibitors or soluble VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:1417831 Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. PMID:7929439 KDR was found to undergo ligand-induced autophosphorylation in intact cells PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | IMP PMID:18614764 Astrocyte responses to injury: VEGF simultaneously modulates... | ACCEPT | Summary: VEGFR2/KDR binding; VEGFR2 is the main signal-transducing receptor. Reason: KDR is a high-affinity VEGF receptor whose ligand-induced autophosphorylation drives chemotaxis and mitogenesis; rat studies show VEGF effects blocked by VEGFR2 kinase inhibitors or soluble VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:1417831 Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. PMID:7929439 KDR was found to undergo ligand-induced autophosphorylation in intact cells PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | ISO GO_REF:0000121 | ACCEPT | Summary: VEGFR2/KDR binding; VEGFR2 is the main signal-transducing receptor. Reason: KDR is a high-affinity VEGF receptor whose ligand-induced autophosphorylation drives chemotaxis and mitogenesis; rat studies show VEGF effects blocked by VEGFR2 kinase inhibitors or soluble VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:1417831 Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. PMID:7929439 KDR was found to undergo ligand-induced autophosphorylation in intact cells PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | ISO GO_REF:0000121 | ACCEPT | Summary: VEGFR2/KDR binding; VEGFR2 is the main signal-transducing receptor. Reason: KDR is a high-affinity VEGF receptor whose ligand-induced autophosphorylation drives chemotaxis and mitogenesis; rat studies show VEGF effects blocked by VEGFR2 kinase inhibitors or soluble VEGFR2. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. PMID:1417831 Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. PMID:7929439 KDR was found to undergo ligand-induced autophosphorylation in intact cells PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. |
| GO:0043410 positive regulation of MAPK cascade | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of MAPK cascade downstream of VEGFR2. Reason: VEGFR2 activates PLCgamma-PKC-ERK; a downstream consequence of the core receptor activation. Supporting Evidence: PMID:18059339 VEGF induced a rapid increase in Egr-dependent transcriptional activation mediated via its major signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway |
| GO:0043410 positive regulation of MAPK cascade | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of MAPK cascade downstream of VEGFR2. Reason: VEGFR2 activates PLCgamma-PKC-ERK; a downstream consequence of the core receptor activation. Supporting Evidence: PMID:18059339 VEGF induced a rapid increase in Egr-dependent transcriptional activation mediated via its major signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway |
| GO:0043524 negative regulation of neuron apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of neuron apoptotic process (neuroprotection). Reason: Negative regulation of neuron apoptotic process (neuroprotection). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:17591953 VEGF-A exposure resulted in a dose-dependent reduction in retinal neuron apoptosis. |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of blood vessel endothelial cell migration. Reason: Core; as for endothelial cell migration. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0043542 endothelial cell migration | ISO GO_REF:0000121 | MODIFY | Summary: Endothelial cell migration: VEGF-A promotes it. Reason: Lateral correction to GO:0010595 positive regulation of endothelial cell migration, accepted here. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Mouse phenotype is real; refined to the regulation term. Proposed replacements: positive regulation of endothelial cell migration Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0044344 cellular response to fibroblast growth factor stimulus | IEP PMID:18617696 Activation transcription factor-4 induced by fibroblast grow... | KEEP AS NON CORE | Summary: Cellular response to FGF stimulus: FGF-2 induces VEGF-A via ATF-4 in rat VSMC. Reason: Expression-response evidence; peripheral. Supporting Evidence: PMID:18617696 Injury also activates vascular endothelial growth factor (VEGF)-A, whose expression is stimulated by ATF-4 overexpression and exposure to FGF-2. |
| GO:0045599 negative regulation of fat cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of fat cell differentiation. Reason: Negative regulation of fat cell differentiation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045601 regulation of endothelial cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of endothelial cell differentiation. Reason: Regulation of endothelial cell differentiation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045669 positive regulation of osteoblast differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of osteoblast differentiation. Reason: Positive regulation of osteoblast differentiation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:23562340 The therapeutic effect of vascular endothelial growth factor... | ACCEPT | Summary: Positive regulation of angiogenesis. Reason: VEGF-A positively regulates angiogenesis; rat hindlimb ischaemia study shows VEGFA-transduced EPCs promote neovascularisation. Core. Supporting Evidence: PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045766 positive regulation of angiogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: Positive regulation of angiogenesis. Reason: VEGF-A positively regulates angiogenesis; rat hindlimb ischaemia study shows VEGFA-transduced EPCs promote neovascularisation. Core. Supporting Evidence: PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045766 positive regulation of angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of angiogenesis. Reason: VEGF-A positively regulates angiogenesis; rat hindlimb ischaemia study shows VEGFA-transduced EPCs promote neovascularisation. Core. Supporting Evidence: PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045766 positive regulation of angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of angiogenesis. Reason: VEGF-A positively regulates angiogenesis; rat hindlimb ischaemia study shows VEGFA-transduced EPCs promote neovascularisation. Core. Supporting Evidence: PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045766 positive regulation of angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of angiogenesis. Reason: VEGF-A positively regulates angiogenesis; rat hindlimb ischaemia study shows VEGFA-transduced EPCs promote neovascularisation. Core. Supporting Evidence: PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045766 positive regulation of angiogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of angiogenesis. Reason: VEGF-A positively regulates angiogenesis; rat hindlimb ischaemia study shows VEGFA-transduced EPCs promote neovascularisation. Core. Supporting Evidence: PMID:23562340 VEGFA-modified EPC and HO-1-modified EPC synergized with each other in promoting angiogenesis in ischemic limbs of rat hindlimb ischemia model. file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045779 negative regulation of bone resorption | IMP PMID:15312247 Increase of both angiogenesis and bone mass in response to e... | KEEP AS NON CORE | Summary: Negative regulation of bone resorption: anti-VEGF prevented the exercise-induced decline in osteoclastic surfaces. Reason: Rat IMP; indirect effect via bone angiogenesis; non-core. Supporting Evidence: PMID:15312247 VEGF blockade in 5-week trained rats fully prevented the exercise-induced increase in metaphyseal BMD PMID:15312247 osteoclastic surfaces continued to decline compared with both sedentary and anti-VEGF-treated running rats |
| GO:0045785 positive regulation of cell adhesion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of cell adhesion. Reason: Positive regulation of cell adhesion. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:12881220 Hypoxia induces myocyte-dependent COX-2 regulation in endoth... | MARK AS OVER ANNOTATED | Summary: Positive regulation of transcription by RNA polymerase II: VEGF induces target genes only indirectly via receptor signalling. Reason: In the rat IDA (PMID:12881220) VEGF from hypoxic myocytes induced endothelial COX-2 transcription; this is a downstream consequence of VEGFR signalling (via PKC and NOS), not a transcription-regulating activity of the ligand. The same holds for the ISO rows (e.g. Egr3 induction, PMID:18059339). Supporting Evidence: PMID:12881220 VEGF induced endothelial cell COX-2 expression by both increasing COX-2 transcription and prolonging the COX-2 mRNA half-life. PMID:18059339 VEGF induced a rapid increase in Egr-dependent transcriptional activation mediated via its major signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Positive regulation of transcription by RNA polymerase II: VEGF induces target genes only indirectly via receptor signalling. Reason: In the rat IDA (PMID:12881220) VEGF from hypoxic myocytes induced endothelial COX-2 transcription; this is a downstream consequence of VEGFR signalling (via PKC and NOS), not a transcription-regulating activity of the ligand. The same holds for the ISO rows (e.g. Egr3 induction, PMID:18059339). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS SOURCE BUT NOT TARGET Human sources show VEGF-induced target-gene transcription downstream of VEGFR2; the gene product itself does not regulate transcription. Supporting Evidence: PMID:12881220 VEGF induced endothelial cell COX-2 expression by both increasing COX-2 transcription and prolonging the COX-2 mRNA half-life. PMID:18059339 VEGF induced a rapid increase in Egr-dependent transcriptional activation mediated via its major signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Positive regulation of transcription by RNA polymerase II: VEGF induces target genes only indirectly via receptor signalling. Reason: In the rat IDA (PMID:12881220) VEGF from hypoxic myocytes induced endothelial COX-2 transcription; this is a downstream consequence of VEGFR signalling (via PKC and NOS), not a transcription-regulating activity of the ligand. The same holds for the ISO rows (e.g. Egr3 induction, PMID:18059339). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS SOURCE BUT NOT TARGET Human sources show VEGF-induced target-gene transcription downstream of VEGFR2; the gene product itself does not regulate transcription. UniProtKB:P15692-4 · human VEGFA isoform VEGF121 SUPPORTS SOURCE BUT NOT TARGET Human sources show VEGF-induced target-gene transcription downstream of VEGFR2; the gene product itself does not regulate transcription. Supporting Evidence: PMID:12881220 VEGF induced endothelial cell COX-2 expression by both increasing COX-2 transcription and prolonging the COX-2 mRNA half-life. PMID:18059339 VEGF induced a rapid increase in Egr-dependent transcriptional activation mediated via its major signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: VEGF receptor signaling pathway: VEGF-A is the ligand that initiates it. Reason: VEGF-A binding to VEGFR2/VEGFR1 initiates the pathway; rat studies show VEGF effects blocked by VEGFR2 inhibition (neural precursors) and soluble VEGFR2 (lung permeability). Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: VEGF receptor signaling pathway: VEGF-A is the ligand that initiates it. Reason: VEGF-A binding to VEGFR2/VEGFR1 initiates the pathway; rat studies show VEGF effects blocked by VEGFR2 inhibition (neural precursors) and soluble VEGFR2 (lung permeability). Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IMP PMID:18614764 Astrocyte responses to injury: VEGF simultaneously modulates... | ACCEPT | Summary: VEGF receptor signaling pathway: VEGF-A is the ligand that initiates it. Reason: VEGF-A binding to VEGFR2/VEGFR1 initiates the pathway; rat studies show VEGF effects blocked by VEGFR2 inhibition (neural precursors) and soluble VEGFR2 (lung permeability). Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF receptor signaling pathway: VEGF-A is the ligand that initiates it. Reason: VEGF-A binding to VEGFR2/VEGFR1 initiates the pathway; rat studies show VEGF effects blocked by VEGFR2 inhibition (neural precursors) and soluble VEGFR2 (lung permeability). Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF receptor signaling pathway: VEGF-A is the ligand that initiates it. Reason: VEGF-A binding to VEGFR2/VEGFR1 initiates the pathway; rat studies show VEGF effects blocked by VEGFR2 inhibition (neural precursors) and soluble VEGFR2 (lung permeability). Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF receptor signaling pathway: VEGF-A is the ligand that initiates it. Reason: VEGF-A binding to VEGFR2/VEGFR1 initiates the pathway; rat studies show VEGF effects blocked by VEGFR2 inhibition (neural precursors) and soluble VEGFR2 (lung permeability). Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:12181492 the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:0048018 receptor ligand activity | ISO GO_REF:0000121 | MODIFY | Summary: Receptor ligand activity is correct but less specific than growth factor activity, which the gene also carries. Reason: GO:0008083 growth factor activity is_a GO:0048018 receptor ligand activity (checked with OAK), and growth factor activity is accepted for this gene on IDA, IBA and ISO evidence. The receptor-ligand claim is correct; the row is refined to the more specific term already carried. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS TRANSFER Donor VEGFA annotation is sound; transfer is faithful. Only the granularity is refined. Proposed replacements: growth factor activity Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. |
| GO:0048018 receptor ligand activity | ISO GO_REF:0000121 | MODIFY | Summary: Receptor ligand activity is correct but less specific than growth factor activity, which the gene also carries. Reason: GO:0008083 growth factor activity is_a GO:0048018 receptor ligand activity (checked with OAK), and growth factor activity is accepted for this gene on IDA, IBA and ISO evidence. The receptor-ligand claim is correct; the row is refined to the more specific term already carried. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS TRANSFER Donor VEGFA annotation is sound; transfer is faithful. Only the granularity is refined. UniProtKB:P15692-4 · human VEGFA isoform VEGF121 SUPPORTS TRANSFER Donor VEGFA annotation is sound; transfer is faithful. Only the granularity is refined. Proposed replacements: growth factor activity Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:7929439 Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. |
| GO:0048255 mRNA stabilization | IDA PMID:12881220 Hypoxia induces myocyte-dependent COX-2 regulation in endoth... | MARK AS OVER ANNOTATED | Summary: mRNA stabilization: VEGF prolongs COX-2 mRNA half-life indirectly via signalling. Reason: The rat IDA shows VEGF prolongs endothelial COX-2 mRNA half-life; VEGF-A is an extracellular ligand and does not itself stabilise mRNA. This is a distal signalling consequence. Supporting Evidence: PMID:12881220 VEGF induced endothelial cell COX-2 expression by both increasing COX-2 transcription and prolonging the COX-2 mRNA half-life. |
| GO:0048286 lung alveolus development | IMP PMID:16230500 Vascular endothelial growth factor gene therapy increases su... | KEEP AS NON CORE | Summary: Lung alveolus development: VEGF blockade impairs rat alveolarisation. Reason: Rat IMP; alveolarisation depends on VEGF-driven capillary growth. Tissue context, non-core. Supporting Evidence: PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries PMID:16230500 Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development |
| GO:0048469 cell maturation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Cell maturation: vague phenotype-derived term. Reason: Phenotype-derived mouse annotation with no defined cell type; VEGF-A acts as an extracellular cue, and any maturation effect is indirect. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS SOURCE BUT NOT TARGET Mouse phenotype-derived; indirect. |
| GO:0048514 blood vessel morphogenesis | ISO GO_REF:0000121 | MODIFY | Summary: Blood vessel morphogenesis: true but general; refined to angiogenesis and vasculogenesis. Reason: GO:0001525 angiogenesis is part_of/is_a descendant of blood vessel development, as is vasculogenesis (GO:0001570) (checked with OAK). VEGF-A is required for both; the general phenotype-derived term is refined to these two processes. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS TRANSFER Mouse knockout phenotype supports the claim; only granularity is refined. Proposed replacements: angiogenesis vasculogenesis Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0048593 camera-type eye morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Camera-type eye morphogenesis. Reason: Camera-type eye morphogenesis. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0048661 positive regulation of smooth muscle cell proliferation | IMP PMID:14693680 Endogenous VEGF-A is responsible for mitogenic effects of MC... | KEEP AS NON CORE | Summary: Positive regulation of smooth muscle cell proliferation: autocrine VEGF-A mediates MCP-1 mitogenicity in rat VSMC. Reason: Rat IMP with neutralising antibody; non-core target-cell context. Supporting Evidence: PMID:14693680 Endogenous vascular endothelial growth factor-A (VEGF-A) was responsible for the mitogenic activity of MCP-1, because neutralizing anti-VEGF-A antibody inhibited cell proliferation in response to MCP-1. |
| GO:0048666 neuron development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Neuron development. Reason: Neuron development. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0048754 branching morphogenesis of an epithelial tube | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Branching morphogenesis of an epithelial tube. Reason: Branching morphogenesis of an epithelial tube. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0048771 tissue remodeling | IEP PMID:23887904 Exposure to diesel exhaust particulates induces cardiac dysf... | MARK AS OVER ANNOTATED | Summary: Tissue remodeling: cardiac VEGF reduced after diesel exhaust exposure. Reason: Full text shows only a 47% decrease in cardiac VEGF protein after diesel exhaust exposure, alongside remodeling; it does not show VEGF-A participating in tissue remodeling. Supporting Evidence: PMID:23887904 exposure to DEP significantly decreased cardiac VEGF (47% decrease; Table 3 ). |
| GO:0048842 positive regulation of axon extension involved in axon guidance | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of axon extension involved in axon guidance (NRP1-dependent). Reason: Positive regulation of axon extension involved in axon guidance (NRP1-dependent). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration |
| GO:0048842 positive regulation of axon extension involved in axon guidance | ISO NOT GO_REF:0000121 | KEEP AS NON CORE | Summary: NOT annotation, transferred from a mouse short-isoform result: Positive regulation of axon extension involved in axon guidance (NRP1-dependent). Reason: This NOT row derives from mouse isoform PR:Q00731-3 (a short, non-NRP1-binding isoform) while the positive rows on the same term derive from PR:Q00731-2. Both can hold: NRP1-binding heparin-binding isoforms mediate this guidance response and the short isoform does not. The rat ISO row has lost the isoform context. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration |
| GO:0048844 artery morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Artery morphogenesis (arterial specification downstream of VEGF/Notch). Reason: Artery morphogenesis (arterial specification downstream of VEGF/Notch). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0048873 homeostasis of number of cells within a tissue | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Homeostasis of number of cells within a tissue: indirect phenotype. Reason: Mouse mutant phenotype of uncertain mechanism; not a process VEGF-A participates in directly. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103178 · mouse Vegfa SUPPORTS SOURCE BUT NOT TARGET Mouse phenotype-derived; indirect. |
| GO:0050679 positive regulation of epithelial cell proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of epithelial cell proliferation. Reason: Positive regulation of epithelial cell proliferation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0050840 extracellular matrix binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Extracellular matrix binding of the basic VEGF-A isoforms. Reason: VEGF-A188 and part of VEGF-A164 are retained on the extracellular matrix after secretion. Non-core property governing bioavailability. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix PMID:14570917 Here we report that VEGF(165) and VEGF(121) binding to fibronectin also increased at acidic pH |
| GO:0050918 positive chemotaxis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive chemotaxis. Reason: VEGF-A induces directed migration of endothelial cells and leukocytes. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. |
| GO:0050918 positive chemotaxis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive chemotaxis. Reason: VEGF-A induces directed migration of endothelial cells and leukocytes. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. |
| GO:0050927 positive regulation of positive chemotaxis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of positive chemotaxis. Reason: Consistent with chemoattractant activity. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:0050930 induction of positive chemotaxis | IBA GO_REF:0000033 | ACCEPT | Summary: Induction of positive chemotaxis. Reason: Precisely the chemoattractant role of a secreted ligand; conserved across the VEGF family. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. |
| GO:0050930 induction of positive chemotaxis | ISO GO_REF:0000121 | ACCEPT | Summary: Induction of positive chemotaxis. Reason: Precisely the chemoattractant role of a secreted ligand; conserved across the VEGF family. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. |
| GO:0051402 neuron apoptotic process | IMP PMID:17591953 Vascular endothelial growth factor-A is a survival factor fo... | MODIFY | Summary: Neuron apoptotic process: VEGF-A inhibits, not executes, retinal neuron apoptosis. Reason: PMID:17591953 shows VEGF-A reduces retinal neuron apoptosis and its inhibition causes RGC loss; the correct term is negative regulation of neuron apoptotic process (GO:0043524), which the gene already carries. Lateral sign correction. Proposed replacements: negative regulation of neuron apoptotic process Supporting Evidence: PMID:17591953 VEGF-A exposure resulted in a dose-dependent reduction in retinal neuron apoptosis. |
| GO:0051593 response to folic acid | IEP PMID:17482424 Folic acid supplementation affects ROS scavenging enzymes, e... | KEEP AS NON CORE | Summary: Response to folic acid: folate raises Vegf-A mRNA in yolk sacs of diabetic rats. Reason: Expression evidence in a diabetic-embryopathy model; peripheral. Supporting Evidence: PMID:17482424 FA treatment normalized vascular morphology, decreased mRNA levels of all three SOD isoforms and increased Vegf-A mRNA levels |
| GO:0051894 positive regulation of focal adhesion assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of focal adhesion assembly (VEGFR2/NRP1-FAK signalling). Reason: Positive regulation of focal adhesion assembly (VEGFR2/NRP1-FAK signalling). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0051894 positive regulation of focal adhesion assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of focal adhesion assembly (VEGFR2/NRP1-FAK signalling). Reason: Positive regulation of focal adhesion assembly (VEGFR2/NRP1-FAK signalling). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of PI3K/AKT signalling. Reason: VEGFR2-PI3K-AKT signalling mediates endothelial survival; downstream output, non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of PI3K/AKT signalling. Reason: VEGFR2-PI3K-AKT signalling mediates endothelial survival; downstream output, non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0055013 cardiac muscle cell development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cardiac muscle cell development (mouse developmental phenotype). Reason: Cardiac muscle cell development (mouse developmental phenotype). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0060319 primitive erythrocyte differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Primitive erythrocyte differentiation. Reason: Primitive erythrocyte differentiation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0060346 bone trabecula formation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Bone trabecula formation (endochondral ossification requires VEGF-driven invasion). Reason: Bone trabecula formation (endochondral ossification requires VEGF-driven invasion). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0060426 lung vasculature development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lung vasculature development. Reason: Lung vasculature development. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries |
| GO:0060426 lung vasculature development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Lung vasculature development. Reason: Lung vasculature development. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:16230500 VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries |
| GO:0060749 mammary gland alveolus development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mammary gland alveolus development. Reason: Mammary gland alveolus development. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0060754 positive regulation of mast cell chemotaxis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of mast cell chemotaxis (VEGFR1-mediated leukocyte chemotaxis). Reason: Positive regulation of mast cell chemotaxis (VEGFR1-mediated leukocyte chemotaxis). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. |
| GO:0060754 positive regulation of mast cell chemotaxis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of mast cell chemotaxis (VEGFR1-mediated leukocyte chemotaxis). Reason: Positive regulation of mast cell chemotaxis (VEGFR1-mediated leukocyte chemotaxis). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:17082651 VEGF-A (10-500 ng/ml) induced basophil chemotaxis. |
| GO:0060948 cardiac vascular smooth muscle cell development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cardiac vascular smooth muscle cell development (mouse developmental phenotype). Reason: Cardiac vascular smooth muscle cell development (mouse developmental phenotype). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0060977 coronary vasculature morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Coronary vasculature morphogenesis (ARBA; consistent with rat coronary angiogenesis evidence). Reason: Coronary vasculature morphogenesis (ARBA; consistent with rat coronary angiogenesis evidence). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:11397779 Vascular endothelial growth factor and basic fibroblast growth factor differentially modulate early postnatal coronary angiogenesis. |
| GO:0060978 angiogenesis involved in coronary vascular morphogenesis | IMP PMID:11397779 Vascular endothelial growth factor and basic fibroblast grow... | KEEP AS NON CORE | Summary: Angiogenesis involved in coronary vascular morphogenesis (rat postnatal coronary angiogenesis). Reason: Rat IMP (abstract not cached; title states VEGF modulates early postnatal coronary angiogenesis). Specific context of the core angiogenic role; non-core context. Supporting Evidence: PMID:11397779 Vascular endothelial growth factor and basic fibroblast growth factor differentially modulate early postnatal coronary angiogenesis. |
| GO:0060982 coronary artery morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Coronary artery morphogenesis (mouse isoform-specific developmental phenotype). Reason: Coronary artery morphogenesis (mouse isoform-specific developmental phenotype). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0061042 vascular wound healing | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Vascular wound healing. Reason: Vascular wound healing. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0061430 bone trabecula morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Bone trabecula morphogenesis. Reason: Bone trabecula morphogenesis. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of ERK1/ERK2 cascade. Reason: Downstream VEGFR2 output; non-core. Supporting Evidence: PMID:18059339 VEGF induced a rapid increase in Egr-dependent transcriptional activation mediated via its major signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of ERK1/ERK2 cascade. Reason: Downstream VEGFR2 output; non-core. Supporting Evidence: PMID:18059339 VEGF induced a rapid increase in Egr-dependent transcriptional activation mediated via its major signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway |
| GO:0070482 response to oxygen levels | IEP PMID:15885787 Differential expression of vascular endothelial growth facto... | UNDECIDED | Summary: Response to oxygen levels: the cited paper appears to be a human pterygium study. Reason: The cached abstract of PMID:15885787 describes VEGF and VEGFR expression in human pterygium and conjunctiva specimens and does not mention rat material or oxygen manipulation. Full text was not available, so whether a rat experiment underlies this IEP cannot be verified. Supporting Evidence: PMID:15885787 Tissue specimens from 75 patients treated for primary pterygia were analyzed |
| GO:0071260 cellular response to mechanical stimulus | IEP PMID:19012730 Mechanical load induced by glass microspheres releases angio... | KEEP AS NON CORE | Summary: Cellular response to mechanical stimulus: mechanical load induces VEGF mRNA in rat cardiomyocytes. Reason: Full-text IEP evidence in neonatal rat ventricular myocytes; peripheral. Supporting Evidence: PMID:19012730 Based on the finding that VEGF mRNA expression was increased by exposure to microspheres for 24 hrs |
| GO:0071391 cellular response to estrogen stimulus | IEP PMID:17272396 Estrogen-induced activation of hypoxia-inducible factor-1alp... | KEEP AS NON CORE | Summary: Cellular response to estrogen stimulus: ERalpha/HIF-1alpha recruitment to the Vegfa promoter. Reason: Rat uterus expression evidence; peripheral. Supporting Evidence: PMID:17272396 estrogen regulation of VEGF expression in the rat uterus involves rapid recruitment of both estrogen receptor (ER)-alpha and hypoxia-inducible factor (HIF)-1alpha to the VEGF promoter |
| GO:0071456 cellular response to hypoxia | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to hypoxia. Reason: Cellular response to hypoxia. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:12181492 Vascular endothelial growth factor (VEGF) is a hypoxia-inducible secreted protein that interacts with receptor tyrosine kinases on endothelial cells to promote angiogenesis. |
| GO:0071456 cellular response to hypoxia | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to hypoxia. Reason: Cellular response to hypoxia. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:12181492 Vascular endothelial growth factor (VEGF) is a hypoxia-inducible secreted protein that interacts with receptor tyrosine kinases on endothelial cells to promote angiogenesis. |
| GO:0071466 cellular response to xenobiotic stimulus | IEP PMID:22326847 Cancer therapy modulates VEGF signaling and viability in adu... | KEEP AS NON CORE | Summary: Cellular response to xenobiotic stimulus: doxorubicin increases VEGF-A release from cardiac endothelial cells. Reason: Expression/release evidence in rat CMEC; peripheral. Supporting Evidence: PMID:22326847 Endothelial cells up-regulated VEGF-A release after peroxide or Doxo treatment. |
| GO:0071542 dopaminergic neuron differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Dopaminergic neuron differentiation. Reason: Dopaminergic neuron differentiation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0071548 response to dexamethasone | IEP PMID:16959835 Glucocorticoids prevent the normal increase in placental vas... | KEEP AS NON CORE | Summary: Response to dexamethasone: glucocorticoids reduce placental Vegf120/188. Reason: Expression-response evidence (IEP) in rat placenta; peripheral to core function. Supporting Evidence: PMID:16959835 dexamethasone-induced fetal and placental growth restriction reduced expression of the Vegf120 and Vegf188 isoforms |
| GO:0071549 cellular response to dexamethasone stimulus | IEP PMID:10215998 Differential downregulation of vascular endothelial growth f... | KEEP AS NON CORE | Summary: Cellular response to dexamethasone: GR-dependent VEGF repression in rat glioma cells. Reason: Expression-response evidence (IEP); peripheral. Supporting Evidence: PMID:10215998 In normoxic C6 and GS9L cells, we observed 50-60% downregulation of VEGF mRNA by dexamethasone |
| GO:0071679 commissural neuron axon guidance | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Commissural neuron axon guidance (VEGF-A/NRP1/FLK1 guidance cue). Reason: Commissural neuron axon guidance (VEGF-A/NRP1/FLK1 guidance cue). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration |
| GO:0071679 commissural neuron axon guidance | ISO NOT GO_REF:0000121 | KEEP AS NON CORE | Summary: NOT annotation, transferred from a mouse short-isoform result: Commissural neuron axon guidance (VEGF-A/NRP1/FLK1 guidance cue). Reason: This NOT row derives from mouse isoform PR:Q00731-3 (a short, non-NRP1-binding isoform) while the positive rows on the same term derive from PR:Q00731-2. Both can hold: NRP1-binding heparin-binding isoforms mediate this guidance response and the short isoform does not. The rat ISO row has lost the isoform context. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of cell migration involved in sprouting angiogenesis. Reason: Core VEGF-A role in tip-cell migration. Supporting Evidence: PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of branching involved in ureteric bud morphogenesis. Reason: Positive regulation of branching involved in ureteric bud morphogenesis. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:0097475 motor neuron migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Motor neuron migration (NRP1-dependent facial motor neuron migration). Reason: Motor neuron migration (NRP1-dependent facial motor neuron migration). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration |
| GO:0097475 motor neuron migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Motor neuron migration (NRP1-dependent facial motor neuron migration). Reason: Motor neuron migration (NRP1-dependent facial motor neuron migration). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration |
| GO:0097533 cellular stress response to acid chemical | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Cellular stress response to acid chemical: VEGF-A is a downstream target of uric acid via KLF2/miR-92a. Reason: The human donor (PMID:26299712) shows high uric acid lowers VEGF-A expression through miR-92a/KLF2 in endothelial cells; VEGF-A is a regulated target in a pathological model, not a participant executing a stress response to acid. Not a conserved role suitable for transfer. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P15692 · human VEGFA SUPPORTS SOURCE BUT NOT TARGET Human BHF-UCL IDA (PMID:26299712) describes VEGF-A as a downstream target of uric-acid-regulated miR-92a/KLF2. |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of cold-induced thermogenesis (adipocyte VEGF-A). Reason: Positive regulation of cold-induced thermogenesis (adipocyte VEGF-A). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:26683794 Loss of VEGF-A in adipocytes, but not macrophages, results in decreased adipose tissue vascularization, with remarkably diminished thermogenic capacity in vivo. |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISS PMID:26683794 Autocrine effect of vascular endothelial growth factor-A is ... | KEEP AS NON CORE | Summary: Positive regulation of cold-induced thermogenesis (adipocyte VEGF-A). Reason: Positive regulation of cold-induced thermogenesis (adipocyte VEGF-A). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:26683794 Loss of VEGF-A in adipocytes, but not macrophages, results in decreased adipose tissue vascularization, with remarkably diminished thermogenic capacity in vivo. |
| GO:0141151 negative regulation of nitric oxide-cGMP mediated signal transduction | ISO GO_REF:0000121 | UNDECIDED | Summary: Negative regulation of NO-cGMP signalling: donor annotation not present in current human GOA. Reason: The human VEGFA GOA file fetched for comparison no longer carries GO:0141151, so the donor cannot be inspected. VEGF-A normally stimulates eNOS/NO production, making a negative effect on NO-cGMP signalling counter-intuitive; left UNDECIDED. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P15692 · human VEGFA SOURCE STALE OR MISSING GO:0141151 is absent from the current human VEGFA GOA file. |
| GO:1900748 positive regulation of vascular endothelial growth factor signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Positive regulation of VEGF signaling pathway: VEGF-A is the pathway ligand, not a regulator of it. Reason: VEGF-A initiates the VEGF signalling pathway (accepted). The human donor (PMID:23688497) concerns miR-15b/VEGFR2 expression in ginsenoside-treated HUVECs, which does not show VEGF-A modulating its own pathway. The regulation term over-states the ligand's role. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P15692 · human VEGFA SOURCE WEAK OR INFERRED Human ComplexPortal IDA from PMID:23688497 is about VEGFR2 regulation by miR-15b, not VEGF-A regulating the pathway. |
| GO:1901165 positive regulation of trophoblast cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of trophoblast cell migration. Reason: Positive regulation of trophoblast cell migration. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:1901492 positive regulation of lymphangiogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of lymphangiogenesis (secondary contribution). Reason: Positive regulation of lymphangiogenesis (secondary contribution). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:1901532 regulation of hematopoietic progenitor cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of hematopoietic progenitor cell differentiation. Reason: Regulation of hematopoietic progenitor cell differentiation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:1902966 positive regulation of protein localization to early endosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of protein localization to early endosome (ligand-induced VEGFR2 trafficking). Reason: Positive regulation of protein localization to early endosome (ligand-induced VEGFR2 trafficking). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: PMID:7929439 KDR was found to undergo ligand-induced autophosphorylation in intact cells |
| GO:1903141 negative regulation of establishment of endothelial barrier | ISO GO_REF:0000121 | ACCEPT | Summary: Negative regulation of establishment of endothelial barrier. Reason: Mechanistic restatement of VEGF-induced permeability (junction disassembly). Core to the permeability function. Supporting Evidence: PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. PMID:16160062 Our findings indicate that VEGF stimulation elicits a robust increase in GEnC permeability. |
| GO:1903392 negative regulation of adherens junction organization | ISO GO_REF:0000121 | ACCEPT | Summary: Negative regulation of adherens junction organization. Reason: VEGF-A induces VE-cadherin phosphorylation and junction disassembly underlying permeability. Core mechanism of permeability. Supporting Evidence: PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:1903589 positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis. Reason: A specific restatement of VEGF-A's core mitogenic role in sprouting; is_a positive regulation of endothelial cell proliferation (checked with OAK). Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:1903589 positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis. Reason: A specific restatement of VEGF-A's core mitogenic role in sprouting; is_a positive regulation of endothelial cell proliferation (checked with OAK). Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:1903672 positive regulation of sprouting angiogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of sprouting angiogenesis. Reason: Core VEGF-A function. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. PMID:21653826 VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis |
| GO:1904568 cellular response to wortmannin | IEP PMID:17272396 Estrogen-induced activation of hypoxia-inducible factor-1alp... | MARK AS OVER ANNOTATED | Summary: Cellular response to wortmannin: wortmannin only blocks estrogen induction of Vegfa. Reason: In PMID:17272396 the PI3K inhibitor prevented estrogen-stimulated VEGF expression; the gene does not respond to wortmannin as a stimulus, the drug was a pathway probe. The response term over-reads the experiment. Supporting Evidence: PMID:17272396 Only PI3K inhibitors, however, blocked E(2) stimulation of VEGF mRNA expression and E(2)-induced uterine edema. |
| GO:1905278 positive regulation of epithelial tube formation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of epithelial tube formation. Reason: Positive regulation of epithelial tube formation. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:1905555 positive regulation of blood vessel branching | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of blood vessel branching. Reason: Consistent with VEGF-A driving sprouting and branching. Core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:1905604 negative regulation of blood-brain barrier permeability | ISO GO_REF:0000121 | MODIFY | Summary: Negative regulation of blood-brain barrier permeability: sign inverted; VEGF-A increases BBB permeability. Reason: The human donor (PMID:19148554, ARUK-UCL IMP) shows VEGF increases brain endothelial permeability and that Ang-1 reverses it, so the anti-permeability effect belongs to ANGPT1. The claim about VEGF-A itself is sound with the opposite sign: VEGF-A is the classic vascular permeability factor (rat in vivo: soluble VEGFR2 prevents I/R lung leak). The row is sign-corrected laterally to positive regulation of blood-brain barrier permeability (GO:1905605), which the gene does not otherwise carry. Propagation Review Root cause: SOURCE BAD Failure modes: REGULATORY SIGN INVERSION Sources checked: UniProtKB:P15692 · human VEGFA SOURCE BAD Human ARUK-UCL IMP from PMID:19148554 has the wrong sign (or wrong gene: ANGPT1). Proposed replacements: positive regulation of blood-brain barrier permeability Supporting Evidence: PMID:19148554 VEGF, one of the key regulators of ischemia-induced vascular permeability, increased endothelial cell permeability in vitro PMID:19148554 Ang-1 reversed this VEGF effect by up-regulating ZO-2 expression PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:1990150 VEGF-A complex | ISO GO_REF:0000121 | ACCEPT | Summary: VEGF-A complex: the disulfide-linked VEGF-A homodimer. Reason: VEGF-A acts as a covalent homodimer (rat protein characterised as a dimeric glycoprotein). Core complex. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt Homodimer; disulfide-linked (PubMed:7706320). PMID:2320579 is a 46-kDa dimeric glycoprotein mitogen |
| GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin | ISO GO_REF:0000121 | ACCEPT | Summary: Negative regulation of cadherin-mediated cell-cell adhesion. Reason: VEGF signalling phosphorylates VE- and E-cadherin and loosens endothelial junctions. Supports the core permeability role. Supporting Evidence: PMID:16793871 Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. |
| GO:2000573 positive regulation of DNA biosynthetic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of DNA biosynthetic process (mitogenic readout). Reason: Positive regulation of DNA biosynthetic process (mitogenic readout). A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
| GO:2001028 positive regulation of endothelial cell chemotaxis | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of endothelial cell chemotaxis. Reason: VEGF-A is the endothelial chemotactic factor. Core. Supporting Evidence: PMID:7929439 The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation |
| GO:2001237 negative regulation of extrinsic apoptotic signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of extrinsic apoptotic signaling pathway. Reason: Negative regulation of extrinsic apoptotic signaling pathway. A real but peripheral, context- or tissue-specific consequence of VEGF-A receptor-ligand signalling (mostly from mouse genetics or orthologous experimental data); retained as non-core. Supporting Evidence: file:rat/Vegfa/Vegfa-uniprot.txt 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. |
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Download this section (compressed HTML)Q: Does rat Vegfa use the conserved upstream CUG start that produces L-VEGF and the N-VEGF fragment in human, and is the rat N-VEGF nuclear under hypoxia? P16612 does not represent this product, yet nucleus/cytoplasm rows are transferred from human N-VEGF.
Q: Should GO:0007200 (PLC-activating GPCR signalling) on human VEGFA (PMID:18059339) be repointed to VEGFR signalling, and GO:1905604 (negative regulation of BBB permeability, PMID:19148554) to the positive term or to ANGPT1?
Q: Is there a rat inhibitory VEGF-Axxxb isoform equivalent to human VEGF165B, which binds KDR without activating signalling?
Q: Should isoform-specific NOT annotations transferred by ISO (mouse PR:Q00731-3 axon-guidance rows) carry the corresponding rat isoform identifier?
Experiment: Isoform-specific knock-in or isoform-restricted rescue in rat (e.g. Vegfa120-only) to test which isoforms mediate NRP1-dependent axon guidance and vessel branching in rat, as in mouse.
Experiment: Ribosome profiling or N-terminal proteomics of hypoxic rat cells to test for CUG-initiated L-VEGF/N-VEGF translation and its subcellular localisation.
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