Search results for VEGFA

Showing 21 results out of 73

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Species

Types

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Protein (3 results from a total of 3)

Identifier: R-HSA-2975974
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: VEGFA: P15692
Identifier: R-HSA-3132764
Species: Homo sapiens
Compartment: platelet alpha granule lumen
Primary external reference: UniProt: VEGFA: P15692
Identifier: R-HSA-4420127
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: VEGFA: P15692-4

Interactor (2 results from a total of 2)

Identifier: EBI-2895491
Species: Homo sapiens
Primary external reference: IntAct: EBI-2895491
Identifier: P15692-12
Species: Homo sapiens
Primary external reference: UniProt: P15692-12

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-5652230
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000112715

Reaction (4 results from a total of 14)

Identifier: R-HSA-1235037
Species: Homo sapiens
Compartment: nucleoplasm, extracellular region
The VEGFA (VEGF) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. Hypoxia-inducible factor binds the VEGF promoter, recruits p300 and CBP, and enhances transcription.
Identifier: R-HSA-9679477
Species: Homo sapiens
Compartment: extracellular region
In normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angiogenesis). In tumor progression, activation of VEGF pathways promotes tumor vascularization, facilitating tumor growth and metastasis. Abnormal VEGF function is also associated with inflammatory diseases including atherosclerosis, and hyperthyroidism. Inhibition of this process may provide clinical benefits to patients suffering from cancer, diabetic macular edema (DME) and age-related macular degeneration (AMD). VEGFA inhibitors are therapeutic options for these diseases (Melincovici et al. 2018, Aguilar-Cazares et al. 2019, Kim et al. 2019).

Aflibercept is a recombinant protein which is indicated for DME, AMD and part of a combined treatment for metastatic colorectal cancer (Chu 2009, Tang & Moore 2013).

Abicipar Pegol (MP0112) is an investigational compound that has been used in trials studying the treatment of DME and AMD (Campochiaro et al. 2013).

Brolucizumab (RTH258, ESBA1008,4) is a monoclonal antibody indicated to treat AMD (Yannuzzi et al. 2019).

Pegaptanib is a polynucleotide aptamer used to treat AMD (Gragoudas et al. 2004, Vinores 2006).

Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. It is indicated for the treatment of DME and AMD (Nguyen et al. 2006, Ferrara et al. 2006).

Vanucizumab is an investigational monoclonal antibody that has been used in trials studying the treatment of colorectal cancer and advanced/metastatic solid tumours (Hidalgo et al. 2018, Bendell et al. 2019).

Bevacizumab (Avastin) is a humanized monoclonal IgG antibody, and inhibits angiogenesis by binding and inhibiting VEGFA (Papachristos et al. 2019). Researchers have identified higher VEGF expression in patients with COVID-19, which may contribute to lung pathologies. Bevacizumab is being investigated for the treatment of lung complications associated with severe cases of COVID-19 (Phase 2/3 NCT04275414) (Rosa & Santos 2020).
Identifier: R-HSA-8864936
Species: Homo sapiens
Compartment: extracellular region, nucleoplasm
Binding of TFAP2A (AP-2 alpha) dimer to AP-2 response elements in the VEGFA gene promoter results in repression of VEGFA expression (Ruiz et al. 2004). CITED2, a transcription co-factor of TFAP2A, also represses VEGFA transcription, but the mechanism has not been established (Li et al. 2012).
Identifier: R-HSA-8864737
Species: Homo sapiens
Compartment: nucleoplasm
TFAP2A (AP-2 alpha) homodimer can associate with AP-2 response elements in the VEGFA gene promoter (Ruiz et al. 2004).

Complex (4 results from a total of 45)

Identifier: R-HSA-195364
Species: Homo sapiens
Compartment: extracellular region
Identifier: R-HSA-4420101
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-4420203
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5218777
Species: Homo sapiens
Compartment: plasma membrane

Set (4 results from a total of 5)

Identifier: R-ALL-9679456
Compartment: extracellular region
Identifier: R-HSA-5357488
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-195393
Species: Homo sapiens
Compartment: extracellular region
Identifier: R-HSA-195389
Species: Homo sapiens
Compartment: extracellular region

Pathway (3 results from a total of 3)

Identifier: R-HSA-4420097
Species: Homo sapiens
Compartment: plasma membrane
Angiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic effect through interaction with transmembrane tyrosine kinase receptors VEGFR, selectively expressed on vascular endothelial cells. VEGFA signaling through VEGFR2 is the major pathway that activates angiogenesis by inducing the proliferation, survival, sprouting and migration of endothelial cells (ECs), and also by increasing endothelial permeability (Lohela et al. 2009, Shibuya & Claesson-Welsh 2006, Claesson-Welsh & Welsh, 2013). The critical role of VEGFR2 in vascular development is highlighted by the fact that VEGFR2-/- mice die at E8.5-9.5 due to defective development of blood islands, endothelial cells and haematopoietic cells (Shalaby et al. 1995).
Identifier: R-HSA-8866910
Species: Homo sapiens
TFAP2A and TFAP2C directly stimulate transcription of the estrogen receptor ESR1 gene (McPherson and Weigel 1999). TFAP2A expression correlates with ESR1 expression in breast cancer, and TFAP2C is frequently overexpressed in estrogen-positive breast cancer and endometrial cancer (deConinck et al. 1995, Turner et al. 1998). TFAP2A, TFAP2C, as well as TFAP2B can directly stimulate the expression of ERBB2, another important breast cancer gene (Bosher et al. 1996). Association of TFAP2A with the YY1 transcription factor significantly increases the ERBB2 transcription rate (Begon et al. 2005). In addition to ERBB2, the expression of another receptor tyrosine kinase, KIT, is also stimulated by TFAP2A and TFAP2B (Huang et al. 1998), while the expression of the VEGF receptor tyrosine kinase ligand VEGFA is repressed by TFAP2A (Ruiz et al. 2004, Li et al. 2012). TFAP2A stimulates transcription of the transforming growth factor alpha (TGFA) gene (Wang et al. 1997). TFAP2C regulates EGFR expression in luminal breast cancer (De Andrade et al. 2016). In placenta, TFAP2A and TFAP2C directly stimulate transcription of both subunits of the human chorionic gonadotropin, CGA and CGB (Johnson et al. 1997, LiCalsi et al. 2000).
Identifier: R-HSA-8864260
Species: Homo sapiens
The AP-2 (TFAP2) family of transcription factors includes five proteins in mammals: TFAP2A (AP-2 alpha), TFAP2B (AP-2 beta), TFAP2C (AP-2 gamma), TFAP2D (AP-2 delta) and TFAP2E (AP-2 epsilon). The AP-2 family transcription factors are evolutionarily conserved in metazoans and are characterized by a helix-span-helix motif at the C-terminus, a central basic region, and the transactivation domain at the N-terminus. The helix-span-helix motif and the basic region enable dimerization and DNA binding (Eckert et al. 2005).

AP-2 dimers bind palindromic GC-rich DNA response elements that match the consensus sequence 5'-GCCNNNGGC-3' (Williams and Tjian 1991a, Williams and Tjian 1991b). Transcriptional co-factors from the CITED family interact with the helix-span-helix (HSH) domain of TFAP2 (AP-2) family of transcription factors and recruit transcription co-activators EP300 (p300) and CREBBP (CBP) to TFAP2-bound DNA elements. CITED2 shows the highest affinity for TFAP2 proteins, followed by CITED4, while CITED1 interacts with TFAP2s with a very low affinity. Mouse embryos defective for CITED2 exhibit neural crest defects, cardiac malformations and adrenal agenesis, which can at least in part be attributed to a defective Tfap2 transactivation (Bamforth et al. 2001, Braganca et al. 2002, Braganca et al. 2003). Transcriptional activity of AP-2 dimers in inhibited by binding of KCTD1 or KCTD15 to the AP-2 transactivation domain (Ding et al. 2009, Zarelli and Dawid 2013). Transcriptional activity of TFAP2A, TFAP2B and TFAP2C is negatively regulated by SUMOylation mediated by UBE2I (UBC9) (Eloranta and Hurst 2002, Berlato et al. 2011, Impens et al. 2014, Bogachek et al. 2014).

During embryonic development, AP-2 transcription factors stimulate proliferation and suppress terminal differentiation in a cell-type specific manner (Eckert et al. 2005).

TFAP2A and TFAP2C directly stimulate transcription of the estrogen receptor ESR1 gene (McPherson and Weigel 1999). TFAP2A expression correlates with ESR1 expression in breast cancer, and TFAP2C is frequently overexpressed in estrogen-positive breast cancer and endometrial cancer (deConinck et al. 1995, Turner et al. 1998). TFAP2A, TFAP2C, as well as TFAP2B can directly stimulate the expression of ERBB2, another important breast cancer gene (Bosher et al. 1996). Association of TFAP2A with the YY1 transcription factor significantly increases the ERBB2 transcription rate (Begon et al. 2005). In addition to ERBB2, the expression of another receptor tyrosine kinase, KIT, is also stimulated by TFAP2A and TFAP2B (Huang et al. 1998), while the expression of the VEGF receptor tyrosine kinase ligand VEGFA is repressed by TFAP2A (Ruiz et al. 2004, Li et al. 2012). TFAP2A stimulates transcription of the transforming growth factor alpha (TGFA) gene (Wang et al. 1997). TFAP2C regulates EGFR in luminal breast cancer (De Andrade et al. 2016).

TFAP2C plays a critical role in maintaining the luminal phenotype in human breast cancer and in influencing the luminal cell phenotype during normal mammary development (Cyr et al. 2015).

In placenta, TFAP2A and TFAP2C directly stimulate transcription of both subunits of the human chorionic gonadotropin, CGA and CGB (Johnson et al. 1997, LiCalsi et al. 2000).

TFAP2A and/or TFAP2C, in complex with CITED2, stimulate transcription of the PITX2 gene, involved in left-right patterning and heart development (Bamforth et al. 2004, Li et al. 2012).

TFAP2A and TFAP2C play opposing roles in transcriptional regulation of the CDKN1A (p21) gene locus. While TFAP2A stimulates transcription of the CDKN1A cyclin-dependent kinase inhibitor (Zeng et al. 1997, Williams et al. 2009, Scibetta et al. 2010), TFAP2C represses CDKN1A transcription (Williams et al. 2009, Scibetta et al. 2010, Wong et al. 2012). Transcription of the TFAP2A gene may be inhibited by CREB and E2F1 (Melnikova et al. 2010).

For review of the AP-2 family of transcription factors, please refer to Eckert et al. 2005.

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