VEGFA (Vascular Endothelial Growth Factor A) is the master regulator of angiogenesis. CRITICAL ISOFORM BIOLOGY: Alternative splicing produces 17 isoforms with diverse functions: (1) Most isoforms (VEGF121/165/189/206) are PRO-ANGIOGENIC, differing in heparin binding and matrix association - VEGF121 is freely diffusible while VEGF189/206 are matrix-bound; (2) VEGF165B (P15692-8) is ANTI-ANGIOGENIC - it binds VEGFR2 but does NOT activate downstream signaling and INHIBITS tumor growth [PMID:15520188]. All current GOA annotations are for positive angiogenesis regulation - MISSING the anti-angiogenic VEGF165B function. This is a case where isoforms have qualitatively different (even opposite) biological effects.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005172 vascular endothelial growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: VEGFA binds to both VEGFR1 (FLT1) and VEGFR2 (KDR) receptors. This is a core molecular function shared by all VEGFA isoforms including VEGF121, VEGF165, VEGF189, VEGF206, and VEGF165B. The UniProt entry explicitly states binding to FLT1/VEGFR1 and KDR/VEGFR2 receptors. Importantly, even the anti-angiogenic VEGF165B isoform binds to KDR/VEGFR2, though it does not activate downstream signaling. The deep research confirms VEGFA binds to VEGFR1 with approximately 50-fold higher affinity than VEGFR2 [VEGFA-deep-research-perplexity.md]. Reason: Core molecular function of VEGFA. All isoforms bind VEGF receptors, making this annotation universally applicable to the gene product. Well-supported by IBA phylogenetic inference and extensive experimental literature. 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. file:human/VEGFA/VEGFA-deep-research-perplexity.md provider: perplexity file:human/VEGFA/VEGFA-deep-research-falcon.md VEGF-A ligands signal mainly through receptor tyrosine kinases **VEGFR1 (FLT1)** and **VEGFR2 (KDR/FLK1)**, with VEGFR2 functioning as the main pro-angiogenic signaling receptor. |
| GO:0008083 growth factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: VEGFA is a canonical growth factor that stimulates endothelial cell proliferation through VEGFR2 signaling. The deep research confirms VEGFA stimulates multiple cellular responses including proliferation, survival, and migration. VEGF165 induces approximately 27% increase in HUVEC proliferation. However, this is true for pro-angiogenic isoforms (VEGF121/165/189/206) but NOT for VEGF165B which lacks mitogenic activity. Reason: Core molecular function. Growth factor activity is well-documented for the major pro-angiogenic isoforms. The IBA inference is phylogenetically sound. Supporting Evidence: PMID:21771332 VEGF stimulated HUVEC proliferation by 27% relative to untreated cells file:human/VEGFA/VEGFA-deep-research-falcon.md VEGF-A is a secreted dimeric growth factor whose primary physiological role is to activate endothelial cells to support vasculogenesis/angiogenesis |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: VEGFA is the canonical ligand that activates VEGF receptor signaling pathways through VEGFR1 and VEGFR2. Binding induces receptor dimerization and autophosphorylation, activating downstream PLCgamma-PKC-MAPK, PI3K-Akt, and p38 MAPK pathways. VEGF165B also binds receptors but initiates only weak signaling insufficient for angiogenic responses [VEGFA-deep-research-perplexity.md]. Reason: Core biological process. VEGFA is the defining ligand for VEGFR signaling pathways. All isoforms engage receptors, though with different downstream consequences. 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 file:human/VEGFA/VEGFA-deep-research-falcon.md VEGFR2 (KDR/FLK1) signaling outputs:** VEGFR2 activation engages multiple canonical pathways: file:human/VEGFA/VEGFA-deep-research-falcon.md Ligand binding triggers receptor **dimerization and transphosphorylation**. |
| GO:0005615 extracellular space | IBA GO_REF:0000033 | ACCEPT | Summary: VEGFA is a secreted growth factor that functions in the extracellular space. It contains an N-terminal signal sequence targeting it to the secretory pathway. However, isoform localization varies: VEGF121 is freely diffusible, VEGF165 has intermediate bioavailability, while VEGF189/206 are matrix-bound. Substantial intracrine functions have also been documented [VEGFA-deep-research-perplexity.md]. Reason: Core cellular component for the secreted protein. While some intracrine signaling exists, the primary function is as an extracellular signaling molecule. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md Canonical VEGF-A isoforms are **secreted** and act predominantly in the **extracellular space** to activate VEGFRs on endothelial cells. |
| GO:0038084 vascular endothelial growth factor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: This is essentially the same as GO:0048010 (vascular endothelial growth factor receptor signaling pathway). VEGFA is the canonical ligand initiating VEGF signaling through VEGFR1/2 receptors. Both pro-angiogenic and anti-angiogenic isoforms participate in this pathway, though with different outcomes. Reason: Core biological process. VEGFA is the defining ligand of the VEGF signaling pathway. Note this term (GO:0038084) is a child of GO:0048010. Supporting Evidence: PMID:20660291 gremlin binds VEGF receptor-2 (VEGFR2), the main transducer of VEGF-mediated angiogenic signals |
| GO:0042056 chemoattractant activity | IBA GO_REF:0000033 | ACCEPT | Summary: VEGFA functions as a chemoattractant for endothelial cells, promoting their directed migration during angiogenesis. It also serves as a chemoattractant for monocytes and macrophages via VEGFR1. The deep research notes VEGF acts as a chemoattractant for endothelial cells and inflammatory cells including macrophages. Reason: Core molecular function. Chemoattractant activity is essential for VEGFA's role in angiogenesis and inflammation. 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: VEGFA induces positive chemotaxis of endothelial cells towards the VEGF source, essential for directed vessel sprouting during angiogenesis. This is mediated primarily through VEGFR2 signaling and downstream Rac1/Cdc42 activation. Reason: Core biological process. Chemotactic guidance of endothelial cells is essential for VEGFA's angiogenic function. 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:0060754 positive regulation of mast cell chemotaxis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: VEGFA can regulate mast cell chemotaxis through VEGFR1 and VEGFR2 expressed on mast cells. This is a peripheral function related to VEGFA's broader roles in inflammation and immune modulation rather than a core angiogenic function. Reason: While VEGFA does regulate immune cell chemotaxis, mast cell chemotaxis is not a core function. This represents a pleiotropic effect in inflammatory contexts. |
| GO:0002040 sprouting angiogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: VEGFA is the master regulator of sprouting angiogenesis. It promotes tip cell selection, endothelial cell migration, proliferation, and vessel lumen formation. CRITICAL ISOFORM NOTE: This applies to pro-angiogenic isoforms (VEGF121/165/189/206) but NOT to VEGF165B, which is anti-angiogenic and inhibits sprouting. Reason: Core function for the majority of VEGFA isoforms. While VEGF165B inhibits angiogenesis, the predominant isoforms are pro-angiogenic. The IBA annotation captures the conserved ancestral function. Isoform-specific annotation would require GO annotation extensions. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md VEGF-A is a secreted dimeric growth factor whose primary physiological role is to activate endothelial cells to support vasculogenesis/angiogenesis (development and remodeling of blood vessels) |
| GO:0001666 response to hypoxia | IBA GO_REF:0000033 | ACCEPT | Summary: VEGFA expression is strongly induced by hypoxia through HIF-1alpha stabilization. This is a key regulatory mechanism ensuring VEGFA is produced when tissues need increased vascularization. The protein itself also has structural adaptations (cystine-knot) enabling proper folding under hypoxic conditions. Reason: Core regulatory relationship. Hypoxia-induced VEGFA expression is one of the most well-characterized gene regulatory responses in mammalian biology. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md VEGFA is a canonical hypoxia-inducible gene regulated by **HIF1Ξ±/HIF2Ξ±** binding to a conserved hypoxia response element |
| GO:0001525 angiogenesis | IEA GO_REF:0000120 | ACCEPT | Summary: VEGFA is the master regulator of angiogenesis. This IEA annotation correctly captures the core function. ISOFORM NOTE: Pro-angiogenic isoforms (VEGF121/165/189/206) promote angiogenesis; VEGF165B is anti-angiogenic. Reason: Core biological process. IEA is consistent with extensive experimental evidence. The term is appropriately general for the gene-level annotation. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md VEGF-A is a secreted dimeric growth factor whose primary physiological role is to activate endothelial cells to support vasculogenesis/angiogenesis (development and remodeling of blood vessels) and to regulate vascular permeability |
| GO:0002376 immune system process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: VEGFA has roles in immune modulation including macrophage chemotaxis and polarization. However, this term is very broad and over-general for the specific immune functions of VEGFA. Reason: While VEGFA does have immune-related functions (macrophage recruitment, M2 polarization), the term "immune system process" is too broad. More specific terms like macrophage chemotaxis would be more informative. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: VEGFA is a secreted growth factor that functions primarily in the extracellular region. Contains an N-terminal signal peptide for secretory pathway targeting. Reason: Core cellular component. VEGFA is secreted and functions extracellularly. This is broader than GO:0005615 (extracellular space) but still accurate. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md Canonical VEGF-A isoforms are **secreted** and act predominantly in the **extracellular space** to activate VEGFRs on endothelial cells. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Nuclear-localized VEGF has been detected in multiple cell types as part of intracrine signaling. The deep research notes nuclear VEGF and VEGFR2 participate in direct regulation of gene expression and metabolic homeostasis. Falcon report additionally documents an N-terminal fragment (N-VEGF) generated by proteolytic cleavage of a hypoxia-induced long form (L-VEGF, from a non-canonical CUG start codon) that is retained intracellularly and translocates to the nucleus, where it induces transcriptional programs including Hif1alpha and VEGF-A isoforms, and is required for normal hypoxia transcriptional responses. Reason: While nuclear VEGFA exists and has functional significance for intracrine signaling (including the N-VEGF nuclear arm of the L-VEGF/N-VEGF axis), the primary localization and function is extracellular. Nuclear localization represents a secondary function specific to N-VEGF proteolytic fragment. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md **N-VEGF** is **retained intracellularly** and can **translocate to the nucleus**. file:human/VEGFA/VEGFA-deep-research-falcon.md forcing N-VEGF into the nucleus (e.g., via NLS fusion) is sufficient to induce transcriptional programs including **Hif1Ξ±** and **VEGF-A isoforms** under normoxia |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: VEGFA transits through the cytoplasm during synthesis and secretion. Intracrine VEGF signaling also involves cytoplasmic pools of VEGF and its receptors. Reason: Cytoplasmic localization is a transit compartment during biosynthesis. The functional localization is extracellular. This is accurate but not a core functional location. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: VEGFA undergoes dimerization and disulfide bond formation in the ER during biosynthesis. The deep research notes that VEGFA can efficiently complete disulfide bond formation in the ER even under hypoxia. Reason: ER is a transit compartment during biosynthesis, not a functional location. Accurate but represents biosynthetic pathway rather than functional localization. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: VEGFA transits through the Golgi for N-linked glycosylation during secretion. Post-Golgi transport depends on glycosylation modifications. Reason: Golgi is a transit compartment for secretion, not a functional location. Accurate but represents biosynthetic pathway. |
| GO:0008083 growth factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: VEGFA is a canonical growth factor stimulating endothelial cell proliferation and survival. This IEA annotation is consistent with the IBA annotation and extensive experimental evidence. Reason: Core molecular function. Duplicates IBA annotation but IEA provides independent computational evidence support. |
| GO:0008201 heparin binding | IEA GO_REF:0000120 | ACCEPT | Summary: Heparin binding is ISOFORM-SPECIFIC. VEGF121 lacks heparin binding (no exons 6/7). VEGF165 has intermediate heparin affinity (exon 7 only). VEGF189/206 have high heparin affinity (exons 6 and 7). This is a key determinant of bioavailability. Reason: Important molecular function, though isoform-specific. The predominant isoforms (VEGF165, VEGF189) do bind heparin. Annotation is valid at gene level. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md Isoform-specific inclusion of heparan-binding features drives different degrees of **extracellular matrix (ECM)/heparan sulfate proteoglycan (HSPG)** binding versus diffusibility. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000117 | ACCEPT | Summary: VEGFA stimulates endothelial cell proliferation through VEGFR2-PLCgamma-PKC-MAPK signaling. Also promotes proliferation of other cell types. ISOFORM NOTE: VEGF165B does not stimulate proliferation. Reason: Core biological process for pro-angiogenic isoforms. Proliferation is essential for angiogenesis. The term is appropriately general. |
| GO:0016020 membrane | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: VEGFA associates with the plasma membrane surface before shedding. The deep research notes substantial fraction localizes to outer plasma membrane in punctate pattern. Reason: Membrane association is transient during secretion. Primary function is extracellular. This InterPro-based annotation is less informative than specific localization terms. |
| GO:0030154 cell differentiation | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: VEGFA promotes endothelial cell differentiation during vascular development and angiogenesis. However, this term is very broad. Reason: While VEGFA affects endothelial cell differentiation, the term is too general. More specific terms like vasculogenesis or endothelial cell differentiation would be more informative. |
| GO:0042056 chemoattractant activity | IEA GO_REF:0000117 | ACCEPT | Summary: VEGFA is a chemoattractant for endothelial cells and monocytes/macrophages. This IEA annotation is consistent with the IBA annotation. Reason: Core molecular function. Duplicates IBA but IEA provides independent evidence support. |
| GO:0043117 positive regulation of vascular permeability | IEA GO_REF:0000117 | ACCEPT | Summary: VEGFA (originally called Vascular Permeability Factor/VPF) is a potent inducer of vascular permeability through phosphorylation of junctional proteins and Rac1-mediated cytoskeletal changes. ISOFORM NOTE: Pro-angiogenic isoforms only. Reason: Core biological process. VEGFA was originally identified as a permeability factor. This is a defining function of the protein. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md to regulate vascular permeability file:human/VEGFA/VEGFA-deep-research-falcon.md **FAK signaling**, linked to ECM adhesion and vascular permeability. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | IEA GO_REF:0000117 | ACCEPT | Summary: VEGFA binds VEGFR2/KDR, the main transducer of angiogenic signals. All isoforms including VEGF165B bind VEGFR2, though with different signaling outcomes. Reason: Core molecular function. VEGFR2 binding is essential for VEGFA signaling. 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. file:human/VEGFA/VEGFA-deep-research-falcon.md with VEGFR2 functioning as the main pro-angiogenic signaling receptor. |
| GO:0045766 positive regulation of angiogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: VEGFA is the master positive regulator of angiogenesis. CRITICAL ISOFORM NOTE: This applies to pro-angiogenic isoforms (VEGF121/165/189/206) but NOT to VEGF165B, which INHIBITS angiogenesis and should have a negative regulation annotation. Reason: Core function for pro-angiogenic isoforms. The annotation correctly captures the predominant function. A separate annotation for VEGF165B anti-angiogenic activity would be needed for completeness. Note: an authoritative 2023 review (Perez-Gutierrez & Ferrara) cited in the Falcon report argues that VEGFxxxb splice variants (including VEGF165b) are better regarded as weak agonists than antagonists, qualifying but not refuting the description-level claim that VEGF165b is anti-angiogenic. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md with VEGFR2 functioning as the main pro-angiogenic signaling receptor. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: VEGFA is the canonical ligand for VEGFR signaling. This IEA annotation is consistent with the IBA annotations for this pathway. Reason: Core biological process. Duplicates IBA but provides independent evidence support. |
| GO:0051781 positive regulation of cell division | IEA GO_REF:0000043 | ACCEPT | Summary: VEGFA promotes endothelial cell division through MAPK signaling. This is related to its proliferative effects. Reason: Valid biological process annotation. Cell division is required for angiogenesis. |
| GO:0005515 protein binding | IPI PMID:10543948 Solution structure of the VEGF-binding domain of Flt-1: comp... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation. VEGFA binds multiple proteins including receptors (VEGFR1, VEGFR2, NRP1), matrix components, and coreceptors. Reason: Protein binding is too generic. More specific binding terms (VEGFR binding, heparin binding) are more informative. This is a common over-annotation pattern. Supporting Evidence: PMID:10543948 Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states. |
| GO:0005515 protein binding | IPI PMID:16763549 Glycosaminoglycan modification of neuropilin-1 modulates VEG... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation based on neuropilin-1 and VEGFR2 interaction studies. Reason: Protein binding is too generic. The specific interaction partners (NRP1, VEGFR2) warrant more specific GO terms. Supporting Evidence: PMID:16763549 Jun 8. Glycosaminoglycan modification of neuropilin-1 modulates VEGFR2 signaling. |
| GO:0005515 protein binding | IPI PMID:17222790 Blocking neuropilin-1 function has an additive effect with a... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation based on neuropilin-1 interaction studies. Reason: Protein binding is too generic. Neuropilin binding would be more informative. Supporting Evidence: PMID:17222790 Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. |
| GO:0005515 protein binding | IPI PMID:20660291 Gremlin is a novel agonist of the major proangiogenic recept... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from Gremlin-VEGFR2 study context. Reason: Protein binding is too generic. Supporting Evidence: PMID:20660291 gremlin binds VEGF receptor-2 (VEGFR2), the main transducer of VEGF-mediated angiogenic signals |
| GO:0005515 protein binding | IPI PMID:21653826 VEGF binding to NRP1 is essential for VEGF stimulation of en... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation based on NRP1 interaction study. Reason: Protein binding is too generic. NRP1 binding would be more informative. Supporting Evidence: PMID:21653826 2011 Jun 8. VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation. |
| GO:0005515 protein binding | IPI PMID:23374253 Endorepellin laminin-like globular 1/2 domains bind Ig3-5 of... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation based on endorepellin-VEGFR2 study. Reason: Protein binding is too generic. Supporting Evidence: PMID:23374253 Endorepellin laminin-like globular 1/2 domains bind Ig3-5 of vascular endothelial growth factor (VEGF) receptor 2 and block pro-angiogenic signaling by VEGFA in endothelial cells. |
| GO:0005515 protein binding | IPI PMID:23583373 Early VEGFR2 activation in response to flow is VEGF-dependen... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation based on VEGFR2 interaction study. Reason: Protein binding is too generic. VEGFR2 binding is already annotated specifically. Supporting Evidence: PMID:23583373 Early VEGFR2 activation in response to flow is VEGF-dependent and mediated by MMP activity. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from proteome-scale interactome study. Reason: Protein binding is too generic for high-throughput interactome data. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:9393862 Crystal structure at 1.7 A resolution of VEGF in complex wit... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from VEGF-Flt1 crystal structure study. Reason: Protein binding is too generic. VEGFR1 binding would be more informative. Supporting Evidence: PMID:9393862 Crystal structure at 1.7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor. |
| GO:0042802 identical protein binding | IPI PMID:12207021 The cystine knot promotes folding and not thermodynamic stab... | ACCEPT | Summary: VEGFA forms homodimers stabilized by interchain disulfide bonds between Cys51 and Cys60. Dimerization is essential for receptor activation. Reason: Core molecular function. VEGFA homodimerization is required for biological activity. This is more specific and informative than generic protein binding. Supporting Evidence: PMID:12207021 2002 Aug 30. The cystine knot promotes folding and not thermodynamic stability in vascular endothelial growth factor. |
| GO:0042802 identical protein binding | IPI PMID:25132001 Development of a highly-potent anti-angiogenic VEGF8-109 het... | ACCEPT | Summary: VEGFA homodimerization study. Consistent with the essential role of dimerization in VEGFA function. Reason: Core molecular function. Homodimerization is essential for VEGFA activity. Supporting Evidence: PMID:25132001 Development of a highly-potent anti-angiogenic VEGF8-109 heterodimer by directed blocking of its VEGFR-2 binding site. |
| GO:0005615 extracellular space | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. VEGFA functions in the extracellular space. Reason: Core cellular component. Consistent with IBA annotation. |
| GO:0010719 negative regulation of epithelial to mesenchymal transition | IEA GO_REF:0000107 | UNDECIDED | Summary: IEA transferred from Ensembl ortholog. The role of VEGFA in EMT is complex and context-dependent. In some contexts VEGFA may inhibit EMT but this is not a well-established core function. Reason: EMT regulation by VEGFA is complex. This ortholog-transferred annotation may not reflect human VEGFA function. Requires literature review. |
| GO:0031290 retinal ganglion cell axon guidance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: VEGFA has documented roles in neural guidance including retinal development. This is a pleiotropic developmental function beyond core angiogenesis. Reason: VEGFA has neural guidance functions but this is peripheral to its core angiogenic role. Valid developmental function. |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | IEA GO_REF:0000107 | REMOVE | Summary: Circular annotation - VEGFA is the stimulus, not the responder. This annotation would be appropriate for VEGF receptors, not VEGFA itself. Reason: Inappropriate annotation. VEGFA is the ligand that causes the stimulus, not a gene product that responds to VEGF stimulus. |
| GO:0048842 positive regulation of axon extension involved in axon guidance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: VEGFA has neural guidance functions including axon extension regulation. This is a pleiotropic developmental function. Reason: Valid developmental function but peripheral to core angiogenic role. |
| GO:0050918 positive chemotaxis | IEA GO_REF:0000107 | ACCEPT | Summary: VEGFA induces positive chemotaxis of endothelial cells and other cell types. Consistent with IBA chemoattractant activity annotation. Reason: Core biological process. Chemotaxis is essential for angiogenesis. |
| GO:0071679 commissural neuron axon guidance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: VEGFA has documented roles in neural guidance. This is a pleiotropic developmental function. Reason: Valid developmental function but peripheral to core angiogenic role. |
| GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: VEGFA has roles in kidney development including ureteric bud morphogenesis. This is a pleiotropic developmental function. Reason: Valid developmental function but peripheral to core angiogenic role. |
| GO:0097475 motor neuron migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: VEGFA has neural guidance functions. Motor neuron migration may be affected by VEGFA signaling as part of developmental neurovascular coordination. Reason: Valid developmental function but peripheral to core angiogenic role. |
| GO:0120162 positive regulation of cold-induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: VEGFA has documented roles in brown adipose tissue function and thermogenesis. The deep research notes autocrine VEGFA is essential for mitochondrial function in brown adipocytes. Reason: Valid metabolic function but peripheral to core angiogenic role. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1235037 | ACCEPT | Summary: Reactome pathway annotation for VEGFA expression. VEGFA is secreted to the extracellular region. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-194310 | ACCEPT | Summary: Reactome pathway annotation for VEGF-A,C,D binding to VEGFR2. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-194311 | ACCEPT | Summary: Reactome pathway annotation for VEGFA,B,PLGF binding to VEGFR1. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-195378 | ACCEPT | Summary: Reactome pathway annotation for homodimerization of VEGF proteins. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420083 | ACCEPT | Summary: Reactome pathway annotation for PTK2 recruitment to VEGFR2 signaling complex. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420099 | ACCEPT | Summary: Reactome pathway annotation for VEGFR2-SHB binding. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420107 | ACCEPT | Summary: Reactome pathway annotation for VEGFR2-SHC2 binding. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420117 | ACCEPT | Summary: Reactome pathway annotation for VEGFR2 autophosphorylation. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420121 | ACCEPT | Summary: Reactome pathway annotation for SFK phosphorylation of PLCgamma1. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420128 | ACCEPT | Summary: Reactome pathway annotation for SRC-1 phosphorylation of SHB. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420140 | ACCEPT | Summary: Reactome pathway annotation for SRC-1 recruitment to VEGFR2. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420143 | ACCEPT | Summary: Reactome pathway annotation for VEGFR2-SH2D2A binding. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420153 | ACCEPT | Summary: Reactome pathway annotation for VEGFR2-PLCgamma1 binding. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420202 | ACCEPT | Summary: Reactome pathway annotation for PLCgamma1 translocation to plasma membrane. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4420206 | ACCEPT | Summary: Reactome pathway annotation. VEGFA is secreted extracellularly. Reason: Core cellular component. Consistent with other annotations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-481007 | ACCEPT | Summary: Reactome pathway annotation for platelet degranulation. Reason: Core cellular component. VEGFA is released during platelet degranulation. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218640 | ACCEPT | Summary: Reactome pathway annotation for NRP1-VEGF binding. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218642 | ACCEPT | Summary: Reactome pathway annotation for NRP1-VEGFR signaling complex. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218643 | ACCEPT | Summary: Reactome pathway annotation for VEGF signaling. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218645 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218804 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218806 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218809 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218811 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218812 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218814 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218815 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218818 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218819 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218820 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218822 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218824 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218826 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218830 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218832 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218836 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218838 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218839 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218847 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218851 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5218854 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5357429 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5357432 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5357479 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6789615 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8864936 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9679477 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9691215 | ACCEPT | Summary: Reactome pathway annotation. Reason: Core cellular component. |
| GO:0031093 platelet alpha granule lumen | TAS Reactome:R-HSA-481007 | ACCEPT | Summary: VEGFA is stored in platelet alpha granules and released during platelet degranulation. This contributes to wound healing and vascular repair. Reason: Valid cellular component. Platelet storage is a documented function. |
| GO:0038084 vascular endothelial growth factor signaling pathway | IDA PMID:20660291 Gremlin is a novel agonist of the major proangiogenic recept... | ACCEPT | Summary: Experimental study demonstrating VEGFA activates VEGFR2 signaling. The paper identifies gremlin as a novel VEGFR2 agonist distinct from VEGF family ligands, validating VEGFA as the canonical VEGFR2 ligand. Reason: Core biological process. IDA evidence from direct experimental demonstration. Supporting Evidence: PMID:20660291 gremlin binds VEGF receptor-2 (VEGFR2), the main transducer of VEGF-mediated angiogenic signals |
| GO:0001525 angiogenesis | IDA PMID:21771332 Glioblastoma-derived leptin induces tube formation and growt... | ACCEPT | Summary: Study comparing VEGF and leptin effects on endothelial cells. VEGF (50 ng/mL) stimulated HUVEC proliferation by 27% and tube formation by ~60%. This directly demonstrates VEGFA angiogenic activity. Reason: Core biological process with direct experimental evidence. Supporting Evidence: PMID:21771332 VEGF stimulated HUVEC proliferation by 27% relative to untreated cells |
| GO:0001569 branching involved in blood vessel morphogenesis | IMP PMID:23688497 MicroRNA-15b contributes to ginsenoside-Rg1-induced angiogen... | UNDECIDED | Summary: IMP evidence for VEGFA role in blood vessel branching morphogenesis. Publication not in cache - based on annotation appears to demonstrate VEGFA involvement in vessel branching. Reason: Cached publication (PMID:23688497) is a study of miR-15b/VEGFR-2 regulation in ginsenoside-Rg1-induced angiogenesis, not a direct demonstration of VEGFA's role in vessel branching. Blood vessel branching is consistent with known VEGFA functions, but this specific reference does not provide direct VEGFA evidence. Retained as UNDECIDED. Supporting Evidence: PMID:23688497 Diminishing expression of endogenous miR-15b could increase VEGFR-2 expression and HUVECs migration and tubulogenesis; while over-expression of miR-15b was found to associate with the reduction of VEGFR-2 expression as well as cellular migration and tubulogenesis. |
| GO:0001938 positive regulation of endothelial cell proliferation | IDA PMID:31915155 PI3KΞ΄ as a Novel Therapeutic Target in Pathological Angiogen... | ACCEPT | Summary: IDA evidence for VEGFA stimulating endothelial cell proliferation. Function is well-established from multiple other sources, and the cached abstract directly describes VEGF-induced EC proliferation. Reason: Core function. Function is well-established from multiple IDA and IBA sources; the cached abstract confirms VEGF-induced EC proliferation. Supporting Evidence: PMID:31915155 cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor |
| GO:0038033 positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway | IDA PMID:31915155 PI3KΞ΄ as a Novel Therapeutic Target in Pathological Angiogen... | ACCEPT | Summary: Specific GO term capturing VEGFA-induced endothelial chemotaxis/migration via VEGFR signaling. The cached abstract directly describes VEGF-induced EC migration, consistent with established VEGFA biology. Reason: Resolved from UNDECIDED to ACCEPT for consistency with the GO:0001938 annotation from the same publication (PR #832 review feedback flagged the inconsistent treatment). The cached abstract confirms VEGF-induced EC migration, which underlies this chemotaxis term. Supporting Evidence: PMID:31915155 cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:11461089 Vascular endothelial growth factor (VEGF) upregulates BCL-2 ... | KEEP AS NON CORE | Summary: IMP evidence for VEGFA anti-apoptotic function. VEGFA promotes endothelial cell survival through PI3K-Akt signaling pathway. Reason: Real but non-core: the generic "negative regulation of apoptotic process" reflects downstream PI3K-Akt survival signaling. VEGFA's core/defining output is angiogenesis and endothelial cell proliferation (GO:0001938, retained as core); generic anti-apoptosis is a secondary consequence. Surfaced by the ASSAY_TO_FUNCTION analysis. Supporting Evidence: PMID:11461089 Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells. file:human/VEGFA/VEGFA-deep-research-falcon.md **PI3K β AKT**, supporting survival and contributing to permeability regulation. |
| GO:1900748 positive regulation of vascular endothelial growth factor signaling pathway | IDA PMID:23688497 MicroRNA-15b contributes to ginsenoside-Rg1-induced angiogen... | UNDECIDED | Summary: Autocrine/positive feedback annotation for VEGFA on its own signaling pathway. VEGFA can amplify its own signaling through various mechanisms. Reason: Cached publication (PMID:23688497) addresses miR-15b/VEGFR-2 regulation in ginsenoside-induced angiogenesis rather than directly demonstrating VEGFA positive feedback on its own signaling pathway. Retained as UNDECIDED. Supporting Evidence: PMID:23688497 Diminishing expression of endogenous miR-15b could increase VEGFR-2 expression and HUVECs migration and tubulogenesis; while over-expression of miR-15b was found to associate with the reduction of VEGFR-2 expression as well as cellular migration and tubulogenesis. |
| GO:1905555 positive regulation of blood vessel branching | IDA PMID:20123964 Lipid phosphate phosphatase 3 stabilization of beta-catenin ... | UNDECIDED | Summary: IDA evidence for VEGFA promoting vessel branching. Publication not in cache. Vessel branching is a core VEGFA angiogenic function. Reason: Publication PMID:20123964 not available for verification. Supporting Evidence: PMID:20123964 Feb 1. Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures. |
| GO:0038084 vascular endothelial growth factor signaling pathway | IMP PMID:19148554 Angiopoietin-1 reduces vascular endothelial growth factor-in... | ACCEPT | Summary: IMP evidence for VEGFA in VEGF signaling pathway. Core function established from multiple sources. Reason: Core biological process. VEGFA is the canonical ligand for VEGF signaling; function is well-established from IBA and other IDA sources. Supporting Evidence: PMID:19148554 Angiopoietin-1 reduces vascular endothelial growth factor-induced brain endothelial permeability via upregulation of ZO-2. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | IDA PMID:18059339 The zinc-finger transcription factor, early growth response ... | ACCEPT | Summary: VEGFA activates PLCgamma through VEGFR2 signaling. The study shows VEGF signals through PKC pathway to activate transcription factor Egr3. Reason: Core signaling mechanism. VEGFR2-PLCgamma-PKC is a major VEGFA signaling pathway. 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:0042056 chemoattractant activity | IDA PMID:18059339 The zinc-finger transcription factor, early growth response ... | ACCEPT | Summary: VEGFA promotes endothelial cell migration. The study demonstrates VEGF mediates endothelial cell migration and tubulogenesis through Egr3. Reason: Core molecular function. Direct experimental evidence for chemoattractant activity. Supporting Evidence: PMID:18059339 Inhibition of Egr3 gene expression by RNA interference was effective in inhibiting basal and VEGF-induced Egr3 gene expression, and it also inhibited VEGF-mediated endothelial cell proliferation, migration and tubulogenesis |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IDA PMID:18059339 The zinc-finger transcription factor, early growth response ... | ACCEPT | Summary: Direct evidence that VEGF signals through VEGFR2/KDR to activate PKC pathway. Reason: Core biological process with direct experimental evidence. 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:0035767 endothelial cell chemotaxis | IDA PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | ACCEPT | Summary: Study shows VEGF induces endothelial cell migration through PKD-HSP27 pathway. Knockdown of HSP27 and PKDs markedly inhibited VEGF-induced HUVEC migration. Reason: Core biological process with direct experimental evidence for chemotaxis mechanism. Supporting Evidence: PMID:18440775 Knockdown of HSP27 and PKDs markedly inhibited VEGF-induced HUVEC migration and tubulogenesis |
| GO:0035767 endothelial cell chemotaxis | IDA PMID:21245381 Neuropilin-1 signaling through p130Cas tyrosine phosphorylat... | ACCEPT | Summary: IDA evidence for VEGFA-induced endothelial cell chemotaxis. Consistent with other experimental evidence. Reason: Core function. Endothelial cell chemotaxis is well-established from multiple IDA sources including PMID:18440775. Supporting Evidence: PMID:21245381 Jan 18. Neuropilin-1 signaling through p130Cas tyrosine phosphorylation is essential for growth factor-dependent migration of glioma and endothelial cells. |
| GO:0043410 positive regulation of MAPK cascade | IDA PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | ACCEPT | Summary: VEGF activates MAPK cascade through VEGFR2 signaling. The study demonstrates VEGF-induced PKD activation leads to downstream signaling including ERK/MAPK. Reason: Core signaling pathway. VEGFR2-PLCgamma-PKC-ERK is a major VEGFA signaling cascade. Supporting Evidence: PMID:18440775 VEGF activated Protein Kinase D (PKD) via PKC |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | IDA PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | ACCEPT | Summary: VEGF promotes endothelial cell migration. Study shows PKD-HSP27 pathway mediates VEGF-induced migration and tubulogenesis. Reason: Core biological process. Essential for angiogenesis. Supporting Evidence: PMID:18440775 Knockdown of HSP27 and PKDs markedly inhibited VEGF-induced HUVEC migration and tubulogenesis |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | ACCEPT | Summary: VEGF promotes angiogenesis. Study shows VEGF-induced tubulogenesis via PKD-HSP27 pathway. CRITICAL ISOFORM NOTE: Applies to pro-angiogenic isoforms only; VEGF165B is anti-angiogenic. Reason: Core biological process for pro-angiogenic isoforms. Supporting Evidence: PMID:18440775 PKDs and HSP27 play major roles in the angiogenic response to VEGF |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IDA PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | ACCEPT | Summary: VEGF signals through VEGFR2/KDR. Study demonstrates VEGF-induced signaling through PKD pathway. Reason: Core biological process. Supporting Evidence: PMID:18440775 2008 Mar 18. Vascular endothelial growth factor induces heat shock protein (HSP) 27 serine 82 phosphorylation and endothelial tubulogenesis via protein kinase D and independent of p38 kinase. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IDA PMID:21245381 Neuropilin-1 signaling through p130Cas tyrosine phosphorylat... | ACCEPT | Summary: IDA evidence for VEGFR signaling. Core function supported by multiple independent references. Reason: Core function. VEGFR signaling is well-established from multiple sources; additional IDA evidence consistent. Supporting Evidence: PMID:21245381 Jan 18. Neuropilin-1 signaling through p130Cas tyrosine phosphorylation is essential for growth factor-dependent migration of glioma and endothelial cells. |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | IDA PMID:18059339 The zinc-finger transcription factor, early growth response ... | ACCEPT | Summary: VEGF promotes cell migration in sprouting angiogenesis through Egr3-mediated transcriptional regulation. Reason: Core biological process. Supporting Evidence: PMID:18059339 it also inhibited VEGF-mediated endothelial cell proliferation, migration and tubulogenesis |
| GO:0031290 retinal ganglion cell axon guidance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for neural guidance function. VEGFA has documented roles in neurovascular coordination. Reason: Valid developmental function but peripheral to core angiogenic role. |
| GO:0038190 VEGF-activated neuropilin signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: VEGFA binds neuropilin-1 (VEGF165 isoform specifically through exon 7). NRP1 serves as a co-receptor enhancing VEGFR2 signaling. Reason: Important signaling pathway, especially for VEGF165 isoform. Supporting Evidence: file:human/VEGFA/VEGFA-deep-research-falcon.md VEGF-A binds VEGF receptors **VEGFR1 and VEGFR2** and co-receptors **neuropilin-1 (NRP1) and neuropilin-2 (NRP2)**. |
| GO:0042056 chemoattractant activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation consistent with IBA and IDA evidence. Reason: Core molecular function. Multiple evidence sources support this. |
| GO:0048842 positive regulation of axon extension involved in axon guidance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for neural guidance function. Reason: Valid developmental function but peripheral to core angiogenic role. |
| GO:0050918 positive chemotaxis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation consistent with IEA evidence. Reason: Core biological process. |
| GO:0071679 commissural neuron axon guidance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for neural guidance function. Reason: Valid developmental function but peripheral to core angiogenic role. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:19652095 Response gene to complement 32, a novel hypoxia-regulated an... | UNDECIDED | Summary: IMP evidence for VEGFA regulation of transcription. Publication not in cache. VEGFA signaling is known to activate various transcription factors. Reason: Publication PMID:19652095 not available for verification. Supporting Evidence: PMID:19652095 Response gene to complement 32, a novel hypoxia-regulated angiogenic inhibitor. |
| GO:0071456 cellular response to hypoxia | IMP PMID:19652095 Response gene to complement 32, a novel hypoxia-regulated an... | UNDECIDED | Summary: IMP evidence for VEGFA in hypoxia response. VEGFA expression is induced by hypoxia, and it also participates in cellular responses to low oxygen. Reason: Publication PMID:19652095 not available for verification. Supporting Evidence: PMID:19652095 Response gene to complement 32, a novel hypoxia-regulated angiogenic inhibitor. |
| GO:0038084 vascular endothelial growth factor signaling pathway | NAS PMID:23878390 MicroRNA 329 suppresses angiogenesis by targeting CD146. | ACCEPT | Summary: NAS (non-traceable author statement) evidence. Consistent with core function. Reason: Core biological process. VEGFA is the canonical ligand. Supporting Evidence: PMID:23878390 Jul 22. MicroRNA 329 suppresses angiogenesis by targeting CD146. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | NAS PMID:23878390 MicroRNA 329 suppresses angiogenesis by targeting CD146. | KEEP AS NON CORE | Summary: NAS evidence for VEGFA activation of NF-kappaB signaling. VEGFA can activate NF-kappaB through various pathways in endothelial and cancer cells. Reason: Valid signaling pathway but not core to angiogenic function. Supporting Evidence: PMID:23878390 Jul 22. MicroRNA 329 suppresses angiogenesis by targeting CD146. |
| GO:1902894 negative regulation of miRNA transcription | NAS PMID:23878390 MicroRNA 329 suppresses angiogenesis by targeting CD146. | KEEP AS NON CORE | Summary: NAS evidence for VEGFA regulation of miRNA transcription. VEGFA signaling can modulate miRNA expression as part of broader transcriptional effects. Reason: Secondary regulatory effect rather than core function. Supporting Evidence: PMID:23878390 Jul 22. MicroRNA 329 suppresses angiogenesis by targeting CD146. |
| GO:0001938 positive regulation of endothelial cell proliferation | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | ACCEPT | Summary: IDA evidence for VEGFA stimulating EC proliferation. Core function well-established. Reason: Core function. Function is well-established from multiple IDA and IBA sources. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0030297 transmembrane receptor protein tyrosine kinase activator activity | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | ACCEPT | Summary: VEGFA activates VEGFR1 and VEGFR2, which are receptor tyrosine kinases. This is the core molecular function of VEGFA as a ligand. Reason: Core molecular function. VEGFA activates VEGFR tyrosine kinase activity. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | REMOVE | Summary: Circular annotation - VEGFA is the stimulus, not the responder. This annotation would be appropriate for VEGF receptors or downstream effectors, not VEGFA itself. Reason: Inappropriate annotation. VEGFA is the ligand that causes the stimulus, not a gene product that responds to VEGF stimulus. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | ACCEPT | Summary: IDA evidence for VEGFA promoting EC migration. Core function well-established. Reason: Core function. EC migration is well-established from multiple IDA sources. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | UNDECIDED | Summary: IDA evidence for VEGFA regulating transcription. Publication not in cache. Reason: Publication PMID:20497126 not available. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IMP PMID:20497126 Characterization of the biological effects of a novel protei... | ACCEPT | Summary: IMP evidence for VEGFR signaling. Core function supported by multiple independent references. Reason: Core function. VEGFR signaling is well-established from multiple sources; additional IMP evidence consistent. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:2001028 positive regulation of endothelial cell chemotaxis | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | UNDECIDED | Summary: VEGFA induces endothelial cell chemotaxis. This is consistent with chemoattractant activity and sprouting angiogenesis function. Reason: Publication PMID:20497126 not available. Function consistent with other evidence. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0038084 vascular endothelial growth factor signaling pathway | IMP PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulatin... | ACCEPT | Summary: IMP evidence for VEGF signaling. Core function established from multiple sources. Reason: Core biological process. VEGFA is the canonical ligand for VEGF signaling. Supporting Evidence: PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulating potential of mesenchymal stem cells in severe pre-eclampsia. |
| GO:0048018 receptor ligand activity | IMP PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulatin... | ACCEPT | Summary: VEGFA is a receptor ligand for VEGFR1, VEGFR2, and neuropilins. This is a core molecular function. Reason: Core molecular function. VEGFA is the canonical VEGFR ligand. Supporting Evidence: PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulating potential of mesenchymal stem cells in severe pre-eclampsia. file:human/VEGFA/VEGFA-deep-research-falcon.md VEGF-A binds VEGF receptors **VEGFR1 and VEGFR2** and co-receptors **neuropilin-1 (NRP1) and neuropilin-2 (NRP2)**. |
| GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway | IMP PMID:23688497 MicroRNA-15b contributes to ginsenoside-Rg1-induced angiogen... | ACCEPT | Summary: VEGFA activates VEGFR2 signaling. This is the primary signaling receptor for angiogenic effects. Reason: Core biological process. VEGFR2 is the main angiogenic signaling receptor. Supporting Evidence: PMID:23688497 Diminishing expression of endogenous miR-15b could increase VEGFR-2 expression and HUVECs migration and tubulogenesis; while over-expression of miR-15b was found to associate with the reduction of VEGFR-2 expression as well as cellular migration and tubulogenesis. |
| GO:0005515 protein binding | IPI PMID:17446437 Association of ATP1A1 and dear single-nucleotide polymorphis... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation. Reason: Protein binding is too generic. More specific binding terms are more informative. Supporting Evidence: PMID:17446437 Epub 2007 Apr 19. Association of ATP1A1 and dear single-nucleotide polymorphism haplotypes with essential hypertension: sex-specific and haplotype-specific effects. |
| GO:0010629 negative regulation of gene expression | IDA PMID:28977001 MicroRNA-30b controls endothelial cell capillary morphogenes... | UNDECIDED | Summary: IDA evidence for VEGFA negative regulation of gene expression. Publication not in cache. Reason: Publication PMID:28977001 not available. Supporting Evidence: PMID:28977001 eCollection 2017. MicroRNA-30b controls endothelial cell capillary morphogenesis through regulation of transforming growth factor beta 2. |
| GO:0005515 protein binding | IPI PMID:25825981 EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from EMMPRIN study. Reason: Protein binding is too generic. Supporting Evidence: PMID:25825981 EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its activation by VEGF. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | IPI PMID:25825981 EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its... | ACCEPT | Summary: VEGFA binds VEGFR2. Core molecular function shared by all VEGFA isoforms. Reason: Core molecular function. Supporting Evidence: PMID:25825981 EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its activation by VEGF. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IDA PMID:1312256 The fms-like tyrosine kinase, a receptor for vascular endoth... | ACCEPT | Summary: Early IDA evidence for VEGFR signaling. This paper identified Flt-1 as a VEGF receptor. Reason: Core function. Historic paper identifying VEGFR1/Flt-1 as VEGF receptor; VEGFR signaling is well-established. Supporting Evidence: PMID:1312256 The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IDA PMID:7929439 Different signal transduction properties of KDR and Flt1, tw... | ACCEPT | Summary: Classic paper demonstrating VEGF signals through KDR (VEGFR2). Shows VEGF induces chemotaxis and mitogenicity in KDR-expressing cells. Reason: Core biological process with landmark experimental evidence. 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:0043536 positive regulation of blood vessel endothelial cell migration | IMP PMID:23688497 MicroRNA-15b contributes to ginsenoside-Rg1-induced angiogen... | ACCEPT | Summary: IMP evidence for EC migration. Core function well-established. Reason: Core function. EC migration is well-established from multiple IDA sources. Supporting Evidence: PMID:23688497 Diminishing expression of endogenous miR-15b could increase VEGFR-2 expression and HUVECs migration and tubulogenesis; while over-expression of miR-15b was found to associate with the reduction of VEGFR-2 expression as well as cellular migration and tubulogenesis. |
| GO:0061042 vascular wound healing | IMP PMID:23688497 MicroRNA-15b contributes to ginsenoside-Rg1-induced angiogen... | ACCEPT | Summary: VEGFA promotes wound healing through stimulation of angiogenesis. This is a physiological context for VEGFA angiogenic function. Reason: Valid biological process. Wound healing is a key physiological context for angiogenesis. Supporting Evidence: PMID:23688497 Diminishing expression of endogenous miR-15b could increase VEGFR-2 expression and HUVECs migration and tubulogenesis; while over-expression of miR-15b was found to associate with the reduction of VEGFR-2 expression as well as cellular migration and tubulogenesis. |
| GO:1903589 positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis | IMP PMID:30106099 Overexpression of miRβ21 is involved in acute monocytic leuk... | UNDECIDED | Summary: IMP evidence for sprouting angiogenesis. Publication not in cache. Reason: Publication PMID:30106099 not available. Supporting Evidence: PMID:30106099 Aug 6. Overexpression of miRβ21 is involved in acute monocytic leukemiaβassociated angiogenesis by targeting ILβ12. |
| GO:0001569 branching involved in blood vessel morphogenesis | IMP PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulatin... | UNDECIDED | Summary: IMP evidence for vessel branching. Publication not in cache. Reason: Publication PMID:23083510 not available. Supporting Evidence: PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulating potential of mesenchymal stem cells in severe pre-eclampsia. |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | IMP PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulatin... | UNDECIDED | Summary: IMP evidence for migration in sprouting angiogenesis. Publication not in cache. Reason: Publication PMID:23083510 not available. Supporting Evidence: PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulating potential of mesenchymal stem cells in severe pre-eclampsia. |
| GO:1901165 positive regulation of trophoblast cell migration | IMP PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulatin... | KEEP AS NON CORE | Summary: VEGFA promotes trophoblast migration during placental development. This is a developmental function beyond core angiogenesis. Reason: Valid developmental function but peripheral to core angiogenic role. Supporting Evidence: PMID:23083510 miR-16 inhibits the proliferation and angiogenesis-regulating potential of mesenchymal stem cells in severe pre-eclampsia. |
| GO:0010629 negative regulation of gene expression | IMP PMID:19148554 Angiopoietin-1 reduces vascular endothelial growth factor-in... | UNDECIDED | Summary: IMP evidence for gene expression regulation. Publication not in cache. Reason: Publication PMID:19148554 not available. Supporting Evidence: PMID:19148554 Angiopoietin-1 reduces vascular endothelial growth factor-induced brain endothelial permeability via upregulation of ZO-2. |
| GO:1905604 negative regulation of blood-brain barrier permeability | IMP PMID:19148554 Angiopoietin-1 reduces vascular endothelial growth factor-in... | UNDECIDED | Summary: VEGFA effects on BBB are complex. It can both increase and decrease permeability depending on context and isoform. Reason: Publication PMID:19148554 not available. BBB effects are context-dependent. Supporting Evidence: PMID:19148554 Angiopoietin-1 reduces vascular endothelial growth factor-induced brain endothelial permeability via upregulation of ZO-2. |
| GO:0005912 adherens junction | IDA PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeab... | UNDECIDED | Summary: VEGFA affects adherens junction organization as part of permeability regulation. Publication not in cache. Reason: Publication PMID:26598555 not available. Supporting Evidence: PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeability and signaling. |
| GO:0043117 positive regulation of vascular permeability | IDA PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeab... | ACCEPT | Summary: VEGFA (originally VPF) is a potent inducer of vascular permeability. This is a core function. ISOFORM NOTE: Pro-angiogenic isoforms only. Reason: Core biological process. VEGFA was originally identified as VPF. Supporting Evidence: PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeability and signaling. |
| GO:1903392 negative regulation of adherens junction organization | IDA PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeab... | ACCEPT | Summary: VEGFA disrupts adherens junctions to increase permeability. Mechanism involves VE-cadherin phosphorylation and internalization. Reason: Part of permeability regulation mechanism. Supporting Evidence: PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeability and signaling. |
| GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin | IDA PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeab... | ACCEPT | Summary: VEGFA promotes VE-cadherin internalization reducing cell-cell adhesion. Part of permeability regulation. Reason: Part of permeability regulation mechanism. Supporting Evidence: PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeability and signaling. |
| GO:1903141 negative regulation of establishment of endothelial barrier | IDA PMID:20048167 Src-induced tyrosine phosphorylation of VE-cadherin is not s... | ACCEPT | Summary: VEGFA disrupts endothelial barrier function to increase permeability. Related to VPF activity. Reason: Core function related to vascular permeability factor activity. Supporting Evidence: PMID:20048167 2010 Jan 4. Src-induced tyrosine phosphorylation of VE-cadherin is not sufficient to decrease barrier function of endothelial monolayers. |
| 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: VEGFA has roles in brown adipose tissue thermogenesis. ISS evidence from mouse studies. Reason: Valid metabolic function but peripheral to core angiogenic role. Supporting Evidence: PMID:26683794 2015 Sep 25. Autocrine effect of vascular endothelial growth factor-A is essential for mitochondrial function in brown adipocytes. |
| GO:0010749 regulation of nitric oxide mediated signal transduction | IDA PMID:16150726 Thrombospondin-1 inhibits endothelial cell responses to nitr... | ACCEPT | Summary: VEGFA activates eNOS to produce NO, a key mediator of vascular relaxation and permeability. Reason: Important signaling mechanism for VEGFA vascular effects. Supporting Evidence: PMID:16150726 Thrombospondin-1 inhibits endothelial cell responses to nitric oxide in a cGMP-dependent manner. |
| GO:0097533 cellular stress response to acid chemical | IDA PMID:26299712 High concentrations of uric acid inhibit angiogenesis via re... | UNDECIDED | Summary: IDA evidence for acid stress response. Publication not in cache. Reason: Publication PMID:26299712 not available. Supporting Evidence: PMID:26299712 High concentrations of uric acid inhibit angiogenesis via regulation of the KrΓΌppel-like factor 2-vascular endothelial growth factor-A axis by miR-92a. |
| GO:1903672 positive regulation of sprouting angiogenesis | IDA PMID:26299712 High concentrations of uric acid inhibit angiogenesis via re... | ACCEPT | Summary: VEGFA is the master regulator of sprouting angiogenesis. Publication not in cache. Reason: Core biological process. Consistent with extensive evidence. Supporting Evidence: PMID:26299712 High concentrations of uric acid inhibit angiogenesis via regulation of the KrΓΌppel-like factor 2-vascular endothelial growth factor-A axis by miR-92a. |
| GO:1903672 positive regulation of sprouting angiogenesis | IGI PMID:25251394 MicroRNA-377 regulates mesenchymal stem cell-induced angioge... | UNDECIDED | Summary: IGI evidence for sprouting angiogenesis. Publication not in cache. Reason: Publication PMID:25251394 not available. Supporting Evidence: PMID:25251394 eCollection 2014. MicroRNA-377 regulates mesenchymal stem cell-induced angiogenesis in ischemic hearts by targeting VEGF. |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | IGI PMID:24844779 Hypoxia-responsive microRNA-101 promotes angiogenesis via he... | UNDECIDED | Summary: IGI evidence for migration in sprouting angiogenesis. Publication not in cache. Reason: Publication PMID:24844779 not available. Supporting Evidence: PMID:24844779 Epub 2014 Jul 29. Hypoxia-responsive microRNA-101 promotes angiogenesis via heme oxygenase-1/vascular endothelial growth factor axis by targeting cullin 3. |
| GO:1903589 positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis | IGI PMID:24844779 Hypoxia-responsive microRNA-101 promotes angiogenesis via he... | UNDECIDED | Summary: IGI evidence for EC proliferation in sprouting. Publication not in cache. Reason: Publication PMID:24844779 not available. Supporting Evidence: PMID:24844779 Epub 2014 Jul 29. Hypoxia-responsive microRNA-101 promotes angiogenesis via heme oxygenase-1/vascular endothelial growth factor axis by targeting cullin 3. |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | IMP PMID:24865854 Dysregulated miR-361-5p/VEGF axis in the plasma and endothel... | UNDECIDED | Summary: IMP evidence for migration in sprouting. Publication not in cache. Reason: Publication PMID:24865854 not available. Supporting Evidence: PMID:24865854 eCollection 2014. Dysregulated miR-361-5p/VEGF axis in the plasma and endothelial progenitor cells of patients with coronary artery disease. |
| GO:0097475 motor neuron migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for neural guidance function. Reason: Valid developmental function but peripheral to core angiogenic role. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:26268439 p75(NTR)-dependent activation of NF-ΞΊB regulates microRNA-50... | ACCEPT | Summary: VEGFA stimulates cell proliferation through VEGFR2-PLCgamma-PKC-MAPK signaling. Core function for pro-angiogenic isoforms. Reason: Core biological process. Deep research confirms VEGFA promotes endothelial cell proliferation. Pro-angiogenic isoforms only; VEGF165b lacks mitogenic activity. Supporting Evidence: PMID:26268439 p75(NTR)-dependent activation of NF-ΞΊB regulates microRNA-503 transcription and pericyte-endothelial crosstalk in diabetes after limb ischaemia. |
| GO:0001934 positive regulation of protein phosphorylation | IDA PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: VEGFA binding to VEGFR2 induces receptor autophosphorylation and downstream phosphorylation cascades. Reason: Core function. VEGFR2 autophosphorylation at Y1175, Y951, Y1214 initiates downstream signaling cascades (deep research). Supporting Evidence: PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice. |
| GO:0010595 positive regulation of endothelial cell migration | IDA PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: VEGFA promotes endothelial cell migration through Y1214-NCK-p38 MAPK pathway and actin remodeling. Reason: Core function for angiogenesis. Deep research confirms VEGF induces chemotaxis and directed migration via Rac1/Cdc42 activation. Supporting Evidence: PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice. |
| GO:0031334 positive regulation of protein-containing complex assembly | IDA PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | KEEP AS NON CORE | Summary: VEGFA signaling may promote assembly of focal adhesion complexes during cell migration. Reason: Supporting function. VEGF promotes focal adhesion turnover via FAK/paxillin pathway (deep research), but this is downstream of core angiogenic function. Supporting Evidence: PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice. |
| GO:0035148 tube formation | IDA PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: VEGFA is essential for vascular tube formation/tubulogenesis during angiogenesis. Reason: Core function. Deep research extensively documents VEGF role in vasculogenic tubulogenesis and lumen formation. Supporting Evidence: PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice. |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: VEGFA is the master regulator of angiogenesis. ISOFORM NOTE - applies to pro-angiogenic isoforms; VEGF165b is anti-angiogenic. Reason: Core function for pro-angiogenic isoforms. Deep research describes VEGFA as "master regulator of angiogenesis." Supporting Evidence: PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice. |
| GO:0008083 growth factor activity | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | ACCEPT | Summary: VEGFA is a canonical growth factor inducing cell proliferation via VEGFR2 signaling. Reason: Core molecular function. VEGFA functions as a homodimeric growth factor (PMID:7929439, deep research). Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | IDA PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | REMOVE | Summary: Circular annotation - VEGFA IS the stimulus, not the responder. This annotation is logically problematic. Reason: Circular annotation. VEGFA is the stimulus, not a gene responding to VEGF stimulus. This annotation should be on VEGF-responsive genes, not VEGFA itself. Supporting Evidence: PMID:18440775 2008 Mar 18. Vascular endothelial growth factor induces heat shock protein (HSP) 27 serine 82 phosphorylation and endothelial tubulogenesis via protein kinase D and independent of p38 kinase. |
| GO:0042056 chemoattractant activity | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | ACCEPT | Summary: VEGFA is a chemoattractant for endothelial cells and monocytes/macrophages. Reason: Core molecular function. Deep research and PMID:7929439 confirm VEGFA induces chemotaxis in endothelial cells and macrophages. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0050918 positive chemotaxis | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | ACCEPT | Summary: VEGFA induces positive chemotaxis in endothelial cells and other cell types. Reason: Core biological process. PMID:7929439 shows VEGF induces chemotaxis in KDR-expressing cells. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0005515 protein binding | IPI PMID:22020326 MULTIMERIN2 impairs tumor angiogenesis and growth by interfe... | MARK AS OVER ANNOTATED | Summary: Generic protein binding term is uninformative. VEGFA binds specifically to VEGFRs, neuropilins, heparin, fibronectin. Reason: Uninformative term. More specific terms like VEGFR binding, heparin binding capture the actual binding functions. Generic "protein binding" adds no useful information. Supporting Evidence: PMID:22020326 MULTIMERIN2 impairs tumor angiogenesis and growth by interfering with VEGF-A/VEGFR2 pathway. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:18093989 Developmental coronary maturation is disturbed by aberrant c... | UNDECIDED | Summary: VEGF signaling can modulate transcription. Publication not in cache for verification. Reason: Publication PMID:18093989 not available in cache. Cannot verify specific transcriptional regulatory mechanism. Supporting Evidence: PMID:18093989 Dec 18. Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling. |
| GO:0001541 ovarian follicle development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA involved in ovarian follicle development through vascularization. ISS from mouse ortholog. Reason: Pleiotropic developmental process. VEGFA provides vascular support for follicle development but this is secondary to core angiogenic function. |
| GO:0001701 in utero embryonic development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA essential for embryonic vascular development. ISS from mouse studies showing embryonic lethality. Reason: Pleiotropic developmental process. VEGFA is essential for embryonic development primarily through its role in vascular formation. Deep research notes VEGFR2 null mice die at E8.5. |
| GO:0001822 kidney development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA important for kidney vascular development. ISS from mouse ortholog. Reason: Pleiotropic developmental process. VEGFA supports kidney development through angiogenesis. Deep research mentions isoform-specific kidney defects. |
| GO:0002052 positive regulation of neuroblast proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA has neuroprotective and neuroproliferative effects beyond angiogenesis. Reason: Secondary function. VEGFA has documented effects on neural cells but this is not a core function. |
| GO:0003007 heart morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA essential for cardiac vascular development. ISS from mouse studies. Reason: Pleiotropic developmental process. Deep research notes VEGF-dependent cardiovascular morphogenesis starting at E7.5-8.0 in mice. |
| GO:0003151 outflow tract morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA involved in cardiac outflow tract development through vascularization. ISS from mouse. Reason: Pleiotropic developmental process. Secondary to core angiogenic function. |
| GO:0003169 coronary vein morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA involved in coronary vessel development. ISS from mouse studies. Reason: Pleiotropic developmental process. Deep research mentions coronary vein morphogenesis defects in VEGF isoform-specific mice. |
| GO:0007498 mesoderm development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA expressed during mesodermal development supporting vascular formation. Reason: Pleiotropic developmental process. VEGF is expressed in mesoderm but function is through vascularization. |
| GO:0007595 lactation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA involved in mammary gland vascularization during lactation. Reason: Pleiotropic physiological process. Secondary to angiogenic function. |
| GO:0030324 lung development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA essential for lung vascular development. Defects seen in isoform-specific mice. Reason: Pleiotropic developmental process. Deep research notes lung defects in VEGF120/120 mice. |
| GO:0030855 epithelial cell differentiation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: VEGFA may affect epithelial differentiation through paracrine effects. Reason: Indirect effect. VEGFA primarily acts on endothelial cells; effects on epithelium are likely secondary/paracrine. |
| GO:0031077 post-embryonic camera-type eye development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA involved in retinal vascular development. Reason: Pleiotropic developmental process. Deep research notes retinal defects in isoform-specific VEGF mice. |
| GO:0036303 lymph vessel morphogenesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: VEGFA may have limited role in lymphangiogenesis; VEGF-C/VEGFR3 is primary pathway. Reason: VEGF-C and VEGFR3 are the primary lymphangiogenic factors. VEGFA role in lymphangiogenesis is minor compared to its role in blood vessel angiogenesis. |
| GO:0042462 eye photoreceptor cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA may affect photoreceptor development through retinal vascularization. Reason: Pleiotropic developmental process. Likely indirect effect through retinal vascularization. |
| GO:0043129 surfactant homeostasis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: VEGFA may affect lung surfactant through pulmonary vascular development. Reason: Indirect effect. This is likely a secondary consequence of VEGFA role in lung vascular development, not a direct function. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:18093989 Developmental coronary maturation is disturbed by aberrant c... | UNDECIDED | Summary: VEGF signaling activates transcription factors that regulate gene expression. Publication not in cache. Reason: Publication PMID:18093989 not available in cache. Cannot verify specific transcriptional mechanism. Supporting Evidence: PMID:18093989 Dec 18. Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling. |
| GO:0048469 cell maturation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: VEGFA may affect cell maturation in various tissues through vascularization. Reason: Too general. Cell maturation effects are likely indirect through vascular support. |
| GO:0048593 camera-type eye morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA involved in eye vascular development. Reason: Pleiotropic developmental process. VEGFA contributes to eye development through vascularization. |
| GO:0048844 artery morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA essential for arterial vessel development. Reason: Pleiotropic developmental process related to core angiogenic function. Deep research mentions artery defects in isoform-specific mice. |
| GO:0050679 positive regulation of epithelial cell proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: VEGFA primarily acts on endothelial cells; epithelial effects are secondary. Reason: Indirect effect. VEGFA primarily stimulates endothelial cell proliferation, not epithelial. |
| GO:0055013 cardiac muscle cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA supports cardiac development through vascularization. Reason: Pleiotropic developmental process. VEGFA affects cardiomyocyte development indirectly through coronary vascularization. |
| GO:0060319 primitive erythrocyte differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA may affect primitive erythropoiesis during early development. Reason: Pleiotropic developmental process. VEGFA expressed in yolk sac during primitive hematopoiesis. |
| GO:0060749 mammary gland alveolus development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA supports mammary gland development through vascularization. Reason: Pleiotropic developmental process. Indirect effect through vascular support. |
| GO:0060948 cardiac vascular smooth muscle cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA involved in coronary vascular smooth muscle development. Reason: Pleiotropic developmental process related to cardiac vascular development. |
| GO:0060982 coronary artery morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA essential for coronary artery development. Reason: Pleiotropic developmental process. Deep research mentions coronary artery defects in isoform-specific mice. |
| GO:0071542 dopaminergic neuron differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA has neuroprotective effects but primary function is angiogenic. Reason: Secondary function. VEGFA has documented neurotrophic effects but this is not core function. |
| GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA involved in kidney/ureteric bud development through vascularization. Reason: Pleiotropic developmental process. Effect on ureteric bud likely through supporting vascularization. |
| GO:0001938 positive regulation of endothelial cell proliferation | IDA PMID:16489009 Minimal active domain and mechanism of action of the angioge... | ACCEPT | Summary: VEGFA stimulates endothelial cell proliferation. Core function for pro-angiogenic isoforms. Reason: Core function. Multiple lines of evidence support VEGFA-induced endothelial proliferation through VEGFR2 signaling. Supporting Evidence: PMID:16489009 Minimal active domain and mechanism of action of the angiogenesis inhibitor histidine-rich glycoprotein. |
| GO:0051894 positive regulation of focal adhesion assembly | IDA PMID:16489009 Minimal active domain and mechanism of action of the angioge... | KEEP AS NON CORE | Summary: VEGFA signaling promotes focal adhesion assembly during endothelial cell migration. Reason: Supporting function for cell migration. Deep research notes FAK/paxillin pathway involvement. Supporting Evidence: PMID:16489009 Minimal active domain and mechanism of action of the angiogenesis inhibitor histidine-rich glycoprotein. |
| GO:0002042 cell migration involved in sprouting angiogenesis | IDA PMID:20660291 Gremlin is a novel agonist of the major proangiogenic recept... | ACCEPT | Summary: VEGFA is essential for endothelial cell migration during sprouting angiogenesis. Reason: Core function. Deep research extensively documents VEGF role in sprouting angiogenesis and directed endothelial migration. Supporting Evidence: PMID:20660291 2010 Jul 21. Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2. |
| GO:0002092 positive regulation of receptor internalization | IDA PMID:20660291 Gremlin is a novel agonist of the major proangiogenic recept... | KEEP AS NON CORE | Summary: VEGF binding induces VEGFR2 internalization as part of signaling. Reason: Part of VEGFR2 signaling mechanism. Deep research notes neuropilin-1 guides VEGFR2 internalization and recycling. Supporting Evidence: PMID:20660291 2010 Jul 21. Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | IPI PMID:20660291 Gremlin is a novel agonist of the major proangiogenic recept... | ACCEPT | Summary: VEGFA binds VEGFR2 (KDR) to activate angiogenic signaling. Core molecular function. Reason: Core molecular function. Deep research and multiple publications confirm VEGFA-VEGFR2 binding. Supporting Evidence: PMID:20660291 gremlin binds VEGF receptor-2 (VEGFR2), the main transducer of VEGF-mediated angiogenic signals |
| GO:0048018 receptor ligand activity | IPI PMID:20660291 Gremlin is a novel agonist of the major proangiogenic recept... | ACCEPT | Summary: VEGFA functions as a ligand for VEGFR1 and VEGFR2 receptors. Reason: Core molecular function. VEGFA is the canonical ligand for VEGF receptors. Supporting Evidence: PMID:20660291 2010 Jul 21. Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2. |
| GO:0005737 cytoplasm | IDA PMID:17082651 Expression and functions of the vascular endothelial growth ... | KEEP AS NON CORE | Summary: VEGFA is synthesized in cytoplasm before secretion. Deep research notes intracrine VEGF signaling. Reason: Cellular component for synthesis. Primary functional location is extracellular but intracrine signaling also documented. Supporting Evidence: PMID:17082651 Expression and functions of the vascular endothelial growth factors and their receptors in human basophils. |
| GO:0030141 secretory granule | IDA PMID:17082651 Expression and functions of the vascular endothelial growth ... | KEEP AS NON CORE | Summary: VEGFA is stored in secretory granules before release. Reason: Part of secretory pathway. Deep research notes VEGF trafficking through secretory pathway and plasma membrane localization. Supporting Evidence: PMID:17082651 Expression and functions of the vascular endothelial growth factors and their receptors in human basophils. |
| GO:0042056 chemoattractant activity | IDA PMID:21245381 Neuropilin-1 signaling through p130Cas tyrosine phosphorylat... | ACCEPT | Summary: VEGFA is a chemoattractant for endothelial cells and macrophages. Reason: Core molecular function. Multiple independent IDA annotations confirm chemoattractant activity. Supporting Evidence: PMID:21245381 Jan 18. Neuropilin-1 signaling through p130Cas tyrosine phosphorylation is essential for growth factor-dependent migration of glioma and endothelial cells. |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:20497126 Characterization of the biological effects of a novel protei... | ACCEPT | Summary: VEGFA is the master regulator of angiogenesis. ISOFORM NOTE - applies to pro-angiogenic isoforms. Reason: Core biological process. Consistent with other IDA evidence for this term. Supporting Evidence: PMID:20497126 Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:18059339 The zinc-finger transcription factor, early growth response ... | KEEP AS NON CORE | Summary: VEGF signaling activates transcription factors including those regulating gene expression. Reason: Downstream effect of VEGF signaling. VEGF activates ERK/MAPK which translocates to nucleus and activates transcription. Supporting Evidence: PMID:18059339 Dec 3. The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis. |
| GO:0005125 cytokine activity | IDA PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | KEEP AS NON CORE | Summary: VEGFA has cytokine-like activity influencing immune cells via VEGFR1. Reason: Secondary function. VEGFA affects macrophage polarization but primary function is growth factor activity. Supporting Evidence: PMID:18440775 2008 Mar 18. Vascular endothelial growth factor induces heat shock protein (HSP) 27 serine 82 phosphorylation and endothelial tubulogenesis via protein kinase D and independent of p38 kinase. |
| GO:0038091 positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway | IDA PMID:17470632 Vascular endothelial growth factor can signal through platel... | MARK AS OVER ANNOTATED | Summary: VEGFA can cross-activate PDGFR signaling. Overly specific term. Reason: Overly specific/contorted term. VEGFA primarily signals through VEGFRs; PDGFR cross-talk is minor. Supporting Evidence: PMID:17470632 Apr 30. Vascular endothelial growth factor can signal through platelet-derived growth factor receptors. |
| GO:0042056 chemoattractant activity | IDA PMID:18440775 Vascular endothelial growth factor induces heat shock protei... | ACCEPT | Summary: VEGFA is a chemoattractant. Duplicate annotation with different reference. Reason: Core molecular function. Consistent with other chemoattractant annotations. Supporting Evidence: PMID:18440775 2008 Mar 18. Vascular endothelial growth factor induces heat shock protein (HSP) 27 serine 82 phosphorylation and endothelial tubulogenesis via protein kinase D and independent of p38 kinase. |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | IDA PMID:20551324 Erk5 activation elicits a vasoprotective endothelial phenoty... | ACCEPT | Summary: VEGFA promotes endothelial cell migration during sprouting angiogenesis. Reason: Core function. Specific to sprouting angiogenesis, a key VEGFA-dependent process. Supporting Evidence: PMID:20551324 2010 Jun 15. Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4). |
| GO:0030224 monocyte differentiation | IDA PMID:21149635 Monocytic cells derived from human embryonic stem cells and ... | KEEP AS NON CORE | Summary: VEGFA affects monocyte differentiation via VEGFR1 signaling. Reason: Secondary function. VEGFA affects immune cells but this is not a core function. Supporting Evidence: PMID:21149635 2010 Dec 13. Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions. |
| GO:0030225 macrophage differentiation | IDA PMID:21149635 Monocytic cells derived from human embryonic stem cells and ... | KEEP AS NON CORE | Summary: VEGFA promotes M2 macrophage polarization via VEGFR1. Reason: Secondary function. Deep research documents VEGF promotion of M2 polarization but this is not core. Supporting Evidence: PMID:21149635 2010 Dec 13. Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions. |
| GO:0005172 vascular endothelial growth factor receptor binding | IPI PMID:10471394 Characterization of the VEGF binding site on the Flt-1 recep... | ACCEPT | Summary: VEGFA binds to VEGFR1 (Flt-1). Core molecular function. Reason: Core molecular function. Multiple references confirm VEGFR binding. Supporting Evidence: PMID:10471394 Characterization of the VEGF binding site on the Flt-1 receptor. |
| GO:0005172 vascular endothelial growth factor receptor binding | IPI PMID:11513746 Direct identification of a major autophosphorylation site on... | ACCEPT | Summary: VEGFA binds to VEGFRs. Duplicate with different reference. Reason: Core molecular function. Additional reference supporting VEGFR binding. Supporting Evidence: PMID:11513746 Direct identification of a major autophosphorylation site on vascular endothelial growth factor receptor Flt-1 that mediates phosphatidylinositol 3'-kinase binding. |
| GO:0045785 positive regulation of cell adhesion | IDA PMID:19674970 Critical role for GATA3 in mediating Tie2 expression and fun... | KEEP AS NON CORE | Summary: VEGFA promotes cell adhesion, supporting endothelial migration and vessel formation. Reason: Supporting function for angiogenesis. Part of cell migration machinery. Supporting Evidence: PMID:19674970 2009 Aug 12. Critical role for GATA3 in mediating Tie2 expression and function in large vessel endothelial cells. |
| GO:0001938 positive regulation of endothelial cell proliferation | IDA PMID:12714610 Expression and localization of tenomodulin, a transmembrane ... | ACCEPT | Summary: VEGFA stimulates endothelial proliferation. Multiple independent references. Reason: Core function. Consistent with other IDA annotations. Supporting Evidence: PMID:12714610 Expression and localization of tenomodulin, a transmembrane type chondromodulin-I-related angiogenesis inhibitor, in mouse eyes. |
| GO:0042056 chemoattractant activity | IDA PMID:17082651 Expression and functions of the vascular endothelial growth ... | ACCEPT | Summary: VEGFA is a chemoattractant. Additional independent reference. Reason: Core molecular function. Consistent evidence across multiple publications. Supporting Evidence: PMID:17082651 Expression and functions of the vascular endothelial growth factors and their receptors in human basophils. |
| GO:0001938 positive regulation of endothelial cell proliferation | IDA PMID:10022831 Role of alphavbeta3 integrin in the activation of vascular e... | ACCEPT | Summary: VEGFA stimulates endothelial proliferation through VEGFR2. Reason: Core function. Additional independent IDA evidence. Supporting Evidence: PMID:10022831 Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. |
| GO:0010595 positive regulation of endothelial cell migration | IDA PMID:10022831 Role of alphavbeta3 integrin in the activation of vascular e... | ACCEPT | Summary: VEGFA promotes endothelial cell migration through integrin-VEGFR2 cooperation. Reason: Core function. The cited paper is about integrin alphavbeta3 and VEGFR2 activation. Supporting Evidence: PMID:10022831 Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | IPI PMID:10022831 Role of alphavbeta3 integrin in the activation of vascular e... | ACCEPT | Summary: VEGFA binds VEGFR2/KDR. Paper about integrin-VEGFR2 activation. Reason: Core molecular function. Multiple references confirm VEGFA-VEGFR2 binding. Supporting Evidence: PMID:10022831 Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. |
| GO:0045766 positive regulation of angiogenesis | IMP PMID:18275976 Aquaporin 1 is required for hypoxia-inducible angiogenesis i... | ACCEPT | Summary: VEGFA promotes angiogenesis. IMP evidence adds to existing support. Reason: Core function. Multiple lines of evidence support this annotation. Supporting Evidence: PMID:18275976 2008 Jan 3. Aquaporin 1 is required for hypoxia-inducible angiogenesis in human retinal vascular endothelial cells. |
| GO:0071456 cellular response to hypoxia | IDA PMID:10575000 Placenta growth factor and vascular endothelial growth facto... | KEEP AS NON CORE | Summary: VEGFA expression is induced by hypoxia and mediates cellular hypoxic response. Reason: VEGFA is induced BY hypoxia rather than being a direct responder. This describes regulation of VEGFA rather than its function. Supporting Evidence: PMID:10575000 Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes. |
| GO:0001938 positive regulation of endothelial cell proliferation | IDA PMID:18577655 The effects of growth factors on the proliferation and in vi... | ACCEPT | Summary: VEGFA stimulates endothelial proliferation. Additional IDA evidence. Reason: Core function. Consistent with multiple other IDA annotations. Supporting Evidence: PMID:18577655 The effects of growth factors on the proliferation and in vitro angiogenesis of human macular inner choroidal endothelial cells. |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:18577655 The effects of growth factors on the proliferation and in vi... | ACCEPT | Summary: VEGFA is master regulator of angiogenesis. Additional IDA support. Reason: Core function. Consistent evidence across publications. Supporting Evidence: PMID:18577655 The effects of growth factors on the proliferation and in vitro angiogenesis of human macular inner choroidal endothelial cells. |
| GO:0001938 positive regulation of endothelial cell proliferation | ISS GO_REF:0000024 | ACCEPT | Summary: VEGFA stimulates endothelial proliferation. ISS from ortholog. Reason: Core function. Supported by multiple IDA annotations for human. |
| GO:0001938 positive regulation of endothelial cell proliferation | IDA PMID:9202027 Vasoactive peptides modulate vascular endothelial cell growt... | ACCEPT | Summary: VEGFA stimulates endothelial proliferation. Additional IDA evidence. Reason: Core function. Consistent with multiple other annotations. Supporting Evidence: PMID:9202027 Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. |
| GO:0001968 fibronectin binding | IDA PMID:14570917 pH regulates vascular endothelial growth factor binding to f... | ACCEPT | Summary: VEGFA binds fibronectin in the extracellular matrix for storage/presentation. Reason: Functional binding. Deep research notes VEGF binds ECM for storage and controlled release. Supporting Evidence: PMID:14570917 2003 Oct 21. pH regulates vascular endothelial growth factor binding to fibronectin: a mechanism for control of extracellular matrix storage and release. |
| GO:0002687 positive regulation of leukocyte migration | TAS PMID:1312256 The fms-like tyrosine kinase, a receptor for vascular endoth... | KEEP AS NON CORE | Summary: VEGFA promotes leukocyte/monocyte migration through VEGFR1. Reason: Secondary function. VEGFA is chemoattractant for monocytes/macrophages but primary function is angiogenic. Supporting Evidence: PMID:1312256 The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. |
| GO:0005125 cytokine activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: VEGFA has cytokine-like functions affecting immune cells. Reason: Secondary function. VEGFA is primarily a growth factor; cytokine activity is secondary. |
| GO:0005615 extracellular space | ISS GO_REF:0000024 | ACCEPT | Summary: VEGFA is secreted and functions in extracellular space. Reason: Core cellular component. VEGFA is a secreted growth factor acting extracellularly. |
| GO:0005615 extracellular space | IDA PMID:9202027 Vasoactive peptides modulate vascular endothelial cell growt... | ACCEPT | Summary: VEGFA is secreted and detected in extracellular space. Reason: Core cellular component. IDA evidence confirms extracellular localization. Supporting Evidence: PMID:9202027 Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. |
| GO:0008083 growth factor activity | ISS GO_REF:0000024 | ACCEPT | Summary: VEGFA is a canonical growth factor. ISS from ortholog. Reason: Core molecular function. Supported by extensive IDA evidence. |
| GO:0008083 growth factor activity | IDA PMID:9202027 Vasoactive peptides modulate vascular endothelial cell growt... | ACCEPT | Summary: VEGFA is a canonical growth factor stimulating cell proliferation. Reason: Core molecular function. Multiple IDA annotations confirm growth factor activity. Supporting Evidence: PMID:9202027 Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. |
| GO:0008201 heparin binding | IMP PMID:14570917 pH regulates vascular endothelial growth factor binding to f... | ACCEPT | Summary: VEGF isoforms differ in heparin binding affinity. VEGF165 has intermediate, VEGF189/206 high binding. Reason: Core molecular function for ECM-binding isoforms. Deep research documents isoform-specific heparin binding. Supporting Evidence: PMID:14570917 2003 Oct 21. pH regulates vascular endothelial growth factor binding to fibronectin: a mechanism for control of extracellular matrix storage and release. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:7929439 Different signal transduction properties of KDR and Flt1, tw... | ACCEPT | Summary: VEGFA stimulates cell proliferation through VEGFR2 signaling. Reason: Core function. PMID:7929439 demonstrates mitogenic activity in KDR-expressing cells. 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:0008360 regulation of cell shape | IDA PMID:10527820 The effects of angiogenic growth factors on extravillous tro... | KEEP AS NON CORE | Summary: VEGFA induces morphological changes in endothelial cells during migration. Reason: Part of migration response. Cell shape changes support angiogenic cell migration. Supporting Evidence: PMID:10527820 The effects of angiogenic growth factors on extravillous trophoblast invasion and motility. |
| GO:0008360 regulation of cell shape | IDA PMID:7929439 Different signal transduction properties of KDR and Flt1, tw... | KEEP AS NON CORE | Summary: VEGFA induces striking morphological changes via VEGFR2/KDR. Reason: Part of migration response. PMID:7929439 describes actin reorganization and membrane ruffling. 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:0030335 positive regulation of cell migration | IDA PMID:7929439 Different signal transduction properties of KDR and Flt1, tw... | ACCEPT | Summary: VEGFA promotes cell migration/chemotaxis through VEGFR2/KDR. Reason: Core function. PMID:7929439 demonstrates chemotaxis in KDR-expressing cells. 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:0043183 vascular endothelial growth factor receptor 1 binding | IPI PMID:1312256 The fms-like tyrosine kinase, a receptor for vascular endoth... | ACCEPT | Summary: VEGFA binds VEGFR1/Flt-1 with high affinity but weak signaling. Reason: Core molecular function. Deep research confirms VEGFA-VEGFR1 binding with Kd ~16 pM. Supporting Evidence: PMID:1312256 The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | IPI PMID:1417831 Identification of the KDR tyrosine kinase as a receptor for ... | ACCEPT | Summary: VEGFA binds VEGFR2/KDR as the main pro-angiogenic receptor. Reason: Core molecular function. VEGFR2 is the primary angiogenic signaling receptor. Supporting Evidence: PMID:1417831 Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | IDA PMID:9202027 Vasoactive peptides modulate vascular endothelial cell growt... | ACCEPT | Summary: VEGFA promotes endothelial cell migration, essential for angiogenesis. Reason: Core function. More specific than general cell migration term. Supporting Evidence: PMID:9202027 Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. |
| GO:0050840 extracellular matrix binding | IC PMID:14570917 pH regulates vascular endothelial growth factor binding to f... | ACCEPT | Summary: VEGF binds ECM components including fibronectin and heparan sulfate proteoglycans. Reason: Functional binding. Deep research documents ECM binding for VEGF storage and controlled release. Supporting Evidence: PMID:14570917 2003 Oct 21. pH regulates vascular endothelial growth factor binding to fibronectin: a mechanism for control of extracellular matrix storage and release. |
| GO:0050927 positive regulation of positive chemotaxis | IDA PMID:12744932 Vascular endothelial growth factor is a chemoattractant for ... | ACCEPT | Summary: VEGFA induces positive chemotaxis in trophoblast and endothelial cells. Reason: Core function. VEGFA is a well-established chemoattractant. Supporting Evidence: PMID:12744932 Vascular endothelial growth factor is a chemoattractant for trophoblast cells. |
| GO:0050927 positive regulation of positive chemotaxis | IDA PMID:7929439 Different signal transduction properties of KDR and Flt1, tw... | ACCEPT | Summary: VEGFA induces chemotaxis through VEGFR2/KDR. Reason: Core function. PMID:7929439 demonstrates chemotaxis in KDR-expressing cells. Supporting Evidence: PMID:7929439 Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. |
| GO:0005161 platelet-derived growth factor receptor binding | IPI PMID:17470632 Vascular endothelial growth factor can signal through platel... | MARK AS OVER ANNOTATED | Summary: VEGFA may have some PDGFR cross-reactivity. Reason: Minor cross-talk. VEGFA primarily binds VEGFRs; PDGFR binding is not a core function. Supporting Evidence: PMID:17470632 Apr 30. Vascular endothelial growth factor can signal through platelet-derived growth factor receptors. |
| GO:0009986 cell surface | IDA PMID:17470632 Vascular endothelial growth factor can signal through platel... | KEEP AS NON CORE | Summary: VEGFA can localize to cell surface. Deep research notes plasma membrane localization. Reason: Part of secretory pathway. VEGFA is found on cell surface before release. Supporting Evidence: PMID:17470632 Apr 30. Vascular endothelial growth factor can signal through platelet-derived growth factor receptors. |
| GO:0030335 positive regulation of cell migration | IDA PMID:17470632 Vascular endothelial growth factor can signal through platel... | ACCEPT | Summary: VEGFA promotes cell migration. Additional independent reference. Reason: Core function. Consistent with multiple other annotations. Supporting Evidence: PMID:17470632 Apr 30. Vascular endothelial growth factor can signal through platelet-derived growth factor receptors. |
| GO:0001666 response to hypoxia | IDA PMID:16490744 Hypoxic conditions stimulate the production of angiogenin an... | KEEP AS NON CORE | Summary: VEGFA expression is induced by hypoxia via HIF-1. This annotation describes VEGFA regulation. Reason: Describes regulation of VEGFA rather than VEGFA function. VEGFA is a hypoxia-responsive gene. Supporting Evidence: PMID:16490744 2006 Feb 20. Hypoxic conditions stimulate the production of angiogenin and vascular endothelial growth factor by human renal proximal tubular epithelial cells in culture. |
| GO:0005615 extracellular space | IDA PMID:16490744 Hypoxic conditions stimulate the production of angiogenin an... | ACCEPT | Summary: VEGFA is secreted into extracellular space. Reason: Core cellular component. VEGFA functions as an extracellular signaling molecule. Supporting Evidence: PMID:16490744 2006 Feb 20. Hypoxic conditions stimulate the production of angiogenin and vascular endothelial growth factor by human renal proximal tubular epithelial cells in culture. |
| GO:0001525 angiogenesis | IDA PMID:11427521 Vascular endothelial growth factor induces cyclooxygenase-de... | ACCEPT | Summary: VEGFA is essential for angiogenesis. Reason: Core biological process. VEGFA is the master regulator of angiogenesis. Supporting Evidence: PMID:11427521 Vascular endothelial growth factor induces cyclooxygenase-dependent proliferation of endothelial cells via the VEGF-2 receptor. |
| GO:0001570 vasculogenesis | TAS PMID:15015550 Vasculogenesis and angiogenesis. | ACCEPT | Summary: VEGFA is essential for de novo blood vessel formation from vascular progenitors. Reason: Core biological process. Deep research documents VEGF role in vasculogenesis. Supporting Evidence: PMID:15015550 Vasculogenesis and angiogenesis. |
| GO:0007399 nervous system development | TAS PMID:15351965 VEGF: once regarded as a specific angiogenic factor, now imp... | KEEP AS NON CORE | Summary: VEGFA has neurotrophic/neuroprotective effects beyond angiogenesis. Reason: Secondary function. VEGFA affects neural development but primary function is angiogenic. Supporting Evidence: PMID:15351965 VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. |
| GO:0008201 heparin binding | IDA PMID:15001987 Heparin affin regulatory peptide binds to vascular endotheli... | ACCEPT | Summary: VEGF binds heparin. Isoform-specific binding affinity. Reason: Core molecular function. Multiple independent references confirm heparin binding. Supporting Evidence: PMID:15001987 Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis. |
| GO:0031012 extracellular matrix | NAS PMID:14570917 pH regulates vascular endothelial growth factor binding to f... | ACCEPT | Summary: VEGF localizes to extracellular matrix especially longer isoforms. Reason: Functional localization. VEGF189/206 are matrix-bound; matrix serves as VEGF reservoir. Supporting Evidence: PMID:14570917 2003 Oct 21. pH regulates vascular endothelial growth factor binding to fibronectin: a mechanism for control of extracellular matrix storage and release. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:10066377 VEGF prevents apoptosis of human microvascular endothelial c... | KEEP AS NON CORE | Summary: VEGFA promotes endothelial cell survival through PI3K-Akt pathway. Reason: Real but non-core, consistent with the GO:0043066 annotation from PMID:11461089: generic anti-apoptosis is a downstream survival effect of VEGF/Akt signaling rather than VEGFA's core angiogenic function. Supporting Evidence: PMID:10066377 VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. |
| GO:0050930 induction of positive chemotaxis | NAS PMID:12744932 Vascular endothelial growth factor is a chemoattractant for ... | ACCEPT | Summary: NAS evidence for chemotaxis. Consistent with IBA and other evidence. Reason: Core biological process. VEGFA induces chemotaxis in multiple cell types. Supporting Evidence: PMID:12744932 Vascular endothelial growth factor is a chemoattractant for trophoblast cells. |
| GO:0016525 negative regulation of angiogenesis | IDA file:human/VEGFA/VEGFA-deep-research-perplexity.md | NEW | Summary: CRITICAL: The VEGF165B isoform (P15692-8) is ANTI-ANGIOGENIC. It binds VEGFR2 but fails to activate downstream signaling, acting as an endogenous inhibitor of angiogenesis. VEGF165B inhibits VEGF165-induced proliferation, migration, and vasodilatation. In colon carcinoma, VEGF165B inhibits tumor growth by blocking angiogenesis. This function is NOT captured by any existing GOA annotation. Reason: Critical missing annotation. VEGF165B has opposite biological activity to other isoforms. The deep research documents that VEGF165B has anti-angiogenic properties and inhibits tumor growth. This represents a fundamentally different function from the pro-angiogenic isoforms currently annotated. |
| GO:0001569 branching involved in blood vessel morphogenesis | IMP PMID:23688497 MicroRNA-15b contributes to ginsenoside-Rg1-induced angiogen... | UNDECIDED | Summary: Cached publication (PMID:23688497) is a study of miR-15b/VEGFR-2 regulation in ginsenoside-Rg1-induced angiogenesis, not a direct demonstration of VEGFA's role in vessel branching. Blood vessel branching is consistent with known VEGFA functions, but this specific reference does not provide direct VEGFA evidence. Retained as UNDECIDED (parallel to the involved_in entry for the same term). Reason: Cached publication (PMID:23688497) is a study of miR-15b/VEGFR-2 regulation in ginsenoside-Rg1-induced angiogenesis, not a direct demonstration of VEGFA's role in vessel branching. Blood vessel branching is consistent with known VEGFA functions, but this specific reference does not provide direct VEGFA evidence. Retained as UNDECIDED. Supporting Evidence: PMID:23688497 Diminishing expression of endogenous miR-15b could increase VEGFR-2 expression and HUVECs migration and tubulogenesis; while over-expression of miR-15b was found to associate with the reduction of VEGFR-2 expression as well as cellular migration and tubulogenesis. |
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