Target Regulator(s) Information (Transcription Factor)
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T20761 | Target Info | |||
| Target Name | Vascular endothelial growth factor A (VEGFA) | ||||
| Synonyms | Vascular permeability factor; VPF; VEGF-A; VEGF | ||||
| Target Type | Successful Target | ||||
| Gene Name | VEGFA | ||||
| Biochemical Class | Growth factor | ||||
| UniProt ID | |||||
| The Transcription Factors (TFs) Regulating This Target | Top | ||||
|---|---|---|---|---|---|
| TF Name | Hypoxia-inducible factor 1A/1B (HIF-1) heterodimer | ||||
| Classification | Superclass | Basic Domains | |||
| Class | Tal/Twist/Atonal/Hen | ||||
| Family | Factors with PAS domain | ||||
| Regulation Mechanism | Site-directed mutational analysis of theVEGFgenepromoterrevealed that anHIF-1 binding site (HBS) and its downstreamHIF-1 ancillary sequence (HAS) within the HRE are required as cis-elements for the transcriptional activation ofVEGFby either hypoxia or nitric oxide (NO). | [1] | |||
| Evidence Score (E-score) | 2 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [1] | |||
| 2 | Electrophoretic Mobility Shift Assay | [3] | |||
| UniProt ID | |||||
| Sequence |
MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVM
RLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYM GLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSK TFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV TTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTET DDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEP NPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVT VFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYR DTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLAC RLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN |
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| The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes | |||||
| Endothelins/sarafotoxins | [+] 1 Endothelins/sarafotoxins Co-regulated By This TF | + | |||
| 1 | Endothelin-1 (EDN1) | Literature-reported Target | Target Info | [4] | |
| Growth factors | [+] 1 Growth factors Co-regulated By This TF | + | |||
| 1 | Vascular endothelial growth factor A (VEGFA) | Successful Target | Target Info | [1] | |
| Hormones | [+] 1 Hormones Co-regulated By This TF | + | |||
| 1 | Erythropoietin (EPO) | Clinical trial Target | Target Info | [5] | |
| Peptidases | [+] 1 Peptidases Co-regulated By This TF | + | |||
| 1 | Transferrin receptor protein 1 (TFRC) | Clinical trial Target | Target Info | [6] | |
| TF Name | Activator protein 2 (AP-2) homodimer | ||||
| Classification | Superclass | Basic Domains | |||
| Class | bHSH | ||||
| Family | AP-2 | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | A GC-rich TGF alpha-responsive region between -88 bp and -65 bp of the VPF/VEGF promoter is necessary for constitutive and TGF alpha-inducible transcriptional activation.Both AP-2 and EGR1 transcription factors were detected as components of the TGF alpha-inducible protein complex in supershift EMSA studies. | [2] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [2] | |||
| UniProt ID | |||||
| Sequence |
MLWKLTDNIKYEDCEDRHDGTSNGTARLPQLGTVGQSPYTSAPPLSHTPNADFQPPYFPP
PYQPIYPQSQDPYSHVNDPYSLNPLHAQPQPQHPGWPGQRQSQESGLLHTHRGLPHQLSG LDPRRDYRRHEDLLHGPHALSSGLGDLSIHSLPHAIEEVPHVEDPGINIPDQTVIKKGPV SLSKSNSNAVSAIPINKDNLFGGVVNPNEVFCSVPGRLSLLSSTSKYKVTVAEVQRRLSP PECLNASLLGGVLRRAKSKNGGRSLREKLDKIGLNLPAGRRKAANVTLLTSLVEGEAVHL ARDFGYVCETEFPAKAVAEFLNRQHSDPNEQVTRKNMLLATKQICKEFTDLLAQDRSPLG NSRPNPILEPGIQSCLTHFNLISHGFGSPAVCAAVTALQNYLTEALKAMDKMYLSNNPNS HTDNNAKSSDKEEKHRK |
||||
| The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes | |||||
| Apoptosis regulators | [+] 1 Apoptosis regulators Co-regulated By This TF | + | |||
| 1 | Apoptosis regulator Bcl-2 (BCL-2) | Successful Target | Target Info | [7] | |
| Cytokines / Cytokine receptors | [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF | + | |||
| 1 | Interferon-gamma (IFNG) | Successful Target | Target Info | [8] | |
| Ester hydrolases | [+] 1 Ester hydrolases Co-regulated By This TF | + | |||
| 1 | Acetylcholinesterase (AChE) | Successful Target | Target Info | [9] | |
| Growth factors | [+] 1 Growth factors Co-regulated By This TF | + | |||
| 1 | Vascular endothelial growth factor A (VEGFA) | Successful Target | Target Info | [2] | |
| Kinases | [+] 1 Kinases Co-regulated By This TF | + | |||
| 1 | Serine/threonine-protein kinase pim-1 (PIM1) | Clinical trial Target | Target Info | [10] | |
| Oxidoreductases | [+] 3 Oxidoreductases Co-regulated By This TF | + | |||
| 1 | Dopamine beta hydroxylase (DBH) | Clinical trial Target | Target Info | [11] | |
| 2 | Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1) | Clinical trial Target | Target Info | [12] | |
| 3 | Quinone reductase 1 (NQO1) | Clinical trial Target | Target Info | [13] | |
| Peptidases | [+] 2 Peptidases Co-regulated By This TF | + | |||
| 1 | Matrix metalloproteinase-2 (MMP-2) | Successful Target | Target Info | [14] | |
| 2 | Neutral endopeptidase (MME) | Clinical trial Target | Target Info | [15] | |
| Pro-neuropeptides | [+] 1 Pro-neuropeptides Co-regulated By This TF | + | |||
| 1 | Neuropeptide Y (NPY) | Literature-reported Target | Target Info | [16] | |
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Identification of hypoxia-inducible factor 1 ancillary sequence and its function in vascular endothelial growth factor gene induction by hypoxia an... J Biol Chem. 2001 Jan 19;276(3):2292-8. | ||||
| REF 2 | Transforming growth factor-alpha-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation. EMBO J. 1997 Feb 17;16(4):750-9. | ||||
| REF 3 | Upregulated hypoxia-inducible factor-1 DNA binding activity to the vascular endothelial growth factor-A promoter mediates increased vascular permea... Ann Thorac Surg. 2004 May;77(5):1751-5. | ||||
| REF 4 | Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein-1, GATA-2, AND p300/CBP. J Biol Chem. 2001 Apr 20;276(16):12645-53. | ||||
| REF 5 | Transitional change in interaction between HIF-1 and HNF-4 in response to hypoxia. J Hum Genet. 1999;44(5):293-9. | ||||
| REF 6 | Identification of a hypoxia response element in the transferrin receptor gene. J Biol Chem. 1999 Aug 20;274(34):24147-52. | ||||
| REF 7 | The retinoblastoma protein binds the promoter of the survival gene bcl-2 and regulates its transcription in epithelial cells through transcription factor AP-2. Mol Cell Biol. 2002 Nov;22(22):7877-88. | ||||
| REF 8 | The nuclear factor YY1 suppresses the human gamma interferon promoter through two mechanisms: inhibition of AP1 binding and activation of a silence... Mol Cell Biol. 1996 Sep;16(9):4744-53. | ||||
| REF 9 | Transcription factor repression and activation of the human acetylcholinesterase gene. J Biol Chem. 1995 Oct 6;270(40):23511-9. | ||||
| REF 10 | The human Pim-1 gene is selectively transcribed in different hemato-lymphoid cell lines in spite of a G + C-rich housekeeping promoter. Mol Cell Biol. 1990 Apr;10(4):1680-8. | ||||
| REF 11 | Noradrenergic-specific transcription of the dopamine beta-hydroxylase gene requires synergy of multiple cis-acting elements including at least two Phox2a-binding sites. J Neurosci. 1998 Oct 15;18(20):8247-60. | ||||
| REF 12 | The proximal promoter region of the gene encoding human 17beta-hydroxysteroid dehydrogenase type 1 contains GATA, AP-2, and Sp1 response elements: analysis of promoter function in choriocarcinoma cells. Endocrinology. 1997 Aug;138(8):3417-25. | ||||
| REF 13 | AP-2-mediated regulation of human NAD(P)H: quinone oxidoreductase 1 (NQO1) gene expression. Biochem Pharmacol. 1996 Mar 22;51(6):771-8. | ||||
| REF 14 | Repression of a matrix metalloprotease gene by E1A correlates with its ability to bind to cell type-specific transcription factor AP-2. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3088-93. | ||||
| REF 15 | Cloning and functional characterization of the 5' flanking region of the human mitochondrial malic enzyme gene. Regulatory role of Sp1 and AP-2. Eur J Biochem. 2001 May;268(10):3017-27. | ||||
| REF 16 | Transcriptional regulation of the human neuropeptide Y gene by nerve growth factor. J Biol Chem. 1994 Jun 3;269(22):15460-8. | ||||
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