Target Regulator(s) Information (Transcription Factor)
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T23348 | Target Info | |||
| Target Name | von Willebrand factor (VWF) | ||||
| Synonyms | vWF; F8VWF | ||||
| Target Type | Successful Target | ||||
| Gene Name | VWF | ||||
| UniProt ID | |||||
| The Transcription Factors (TFs) Regulating This Target | Top | ||||
|---|---|---|---|---|---|
| TF Name | ETS proto-oncogene 2 (C-ets-2) | ||||
| Classification | Superclass | Helix-turn-helix | |||
| Class | Tryptophan clusters | ||||
| Family | Ets-type | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | The promoter activity of the -60/+19 region of the VWF gene depends on transcription factors of the ETS family of which several members like ETS-1, ETS-2 and Erg are expressed in endothelium. | [1] | |||
| Evidence Score (E-score) | 2 | + | |||
| 1 | #NAME? | [1] | |||
| 2 | Electrophoretic Mobility Shift Assay | [4] | |||
| UniProt ID | |||||
| Sequence |
MNDFGIKNMDQVAPVANSYRGTLKRQPAFDTFDGSLFAVFPSLNEEQTLQEVPTGLDSIS
HDSANCELPLLTPCSKAVMSQALKATFSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATN EFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLEQMIKENQEKTEDQYEE NSHLTSVPHWINSNTLGFGTEQAPYGMQTQNYPKGGLLDSMCPASTPSVLSSEQEFQMFP KSRLSSVSVTYCSVSQDFPGSNLNLLTNNSGTPKDHDSPENGADSFESSDSLLQSWNSQS SLLDVQRVPSFESFEDDCSQSLCLNKPTMSFKDYIQERSDPVEQGKPVIPAAVLAGFTGS GPIQLWQFLLELLSDKSCQSFISWTGDGWEFKLADPDEVARRWGKRKNKPKMNYEKLSRG LRYYYDKNIIHKTSGKRYVYRFVCDLQNLLGFTPEELHAILGVQPDTED |
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| 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 | [5] | |
| Cytokines / Cytokine receptors | [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF | + | |||
| 1 | Interleukin-12 beta (IL12B) | Successful Target | Target Info | [6] | |
| Glycoproteins | [+] 1 Glycoproteins Co-regulated By This TF | + | |||
| 1 | von Willebrand factor (VWF) | Successful Target | Target Info | [1] | |
| Oxidoreductases | [+] 1 Oxidoreductases Co-regulated By This TF | + | |||
| 1 | Nitric-oxide synthase endothelial (NOS3) | Clinical trial Target | Target Info | [7] | |
| TF Name | GATA-binding factor 2 (GATA-2) | ||||
| Classification | Superclass | Zinc-coordinating DNA-binding domains | |||
| Class | diverse Cys4 zinc fingers | ||||
| Family | GATA-Factors | ||||
| Subfamily | vertebral GATA-Factors | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | Mutations in either the SP1 or octamer sequence have no effect on transcriptional activity, while mutation in the GATA binding element totally abolishes the promoter activity. Evidence that a GATA factor is involved in this interaction is presented. Thus, the positive regulatory region with an intact GATA binding site is required to overcome the inhibitory effect of the negative regulatory element and activate vWf gene expression in an endothelial-cell-specific manner. | [2] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [2] | |||
| UniProt ID | |||||
| Sequence |
MEVAPEQPRWMAHPAVLNAQHPDSHHPGLAHNYMEPAQLLPPDEVDVFFNHLDSQGNPYY
ANPAHARARVSYSPAHARLTGGQMCRPHLLHSPGLPWLDGGKAALSAAAAHHHNPWTVSP FSKTPLHPSAAGGPGGPLSVYPGAGGGSGGGSGSSVASLTPTAAHSGSHLFGFPPTPPKE VSPDPSTTGAASPASSSAGGSAARGEDKDGVKYQVSLTESMKMESGSPLRPGLATMGTQP ATHHPIPTYPSYVPAAAHDYSSGLFHPGGFLGGPASSFTPKQRSKARSCSEGRECVNCGA TATPLWRRDGTGHYLCNACGLYHKMNGQNRPLIKPKRRLSAARRAGTCCANCQTTTTTLW RRNANGDPVCNACGLYYKLHNVNRPLTMKKEGIQTRNRKMSNKSKKSKKGAECFEELSKC MQEKSSPFSAAALAGHMAPVGHLPPFSHSGHILPTPTPIHPSSSLSFGHPHPSSMVTAMG |
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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 | [8] | |
| G protein-coupled receptors | [+] 1 G protein-coupled receptors Co-regulated By This TF | + | |||
| 1 | Gonadotropin-releasing hormone receptor (GNRHR) | Successful Target | Target Info | [9] | |
| Glycoproteins | [+] 1 Glycoproteins Co-regulated By This TF | + | |||
| 1 | von Willebrand factor (VWF) | Successful Target | Target Info | [2] | |
| Hormones | [+] 1 Hormones Co-regulated By This TF | + | |||
| 1 | Erythropoietin (EPO) | Clinical trial Target | Target Info | [10] | |
| Oxidoreductases | [+] 2 Oxidoreductases Co-regulated By This TF | + | |||
| 1 | Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1) | Clinical trial Target | Target Info | [11] | |
| 2 | Nitric-oxide synthase endothelial (NOS3) | Clinical trial Target | Target Info | [12] | |
| Transcription factors | [+] 1 Transcription factors Co-regulated By This TF | + | |||
| 1 | Wilms tumor protein (WT1) | Clinical trial Target | Target Info | [13] | |
| TF Name | Erythroid transcription factor (Eryf1) | ||||
| Classification | Superclass | Zinc-coordinating DNA-binding domains | |||
| Class | diverse Cys4 zinc fingers | ||||
| Family | GATA-Factors | ||||
| Subfamily | vertebral GATA-Factors | ||||
| Regulation Type | Increase | ||||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [2] | |||
| UniProt ID | |||||
| Sequence |
MEFPGLGSLGTSEPLPQFVDPALVSSTPESGVFFPSGPEGLDAAASSTAPSTATAAAAAL
AYYRDAEAYRHSPVFQVYPLLNCMEGIPGGSPYAGWAYGKTGLYPASTVCPTREDSPPQA VEDLDGKGSTSFLETLKTERLSPDLLTLGPALPSSLPVPNSAYGGPDFSSTFFSPTGSPL NSAAYSSPKLRGTLPLPPCEARECVNCGATATPLWRRDRTGHYLCNACGLYHKMNGQNRP LIRPKKRLIVSKRAGTQCTNCQTTTTTLWRRNASGDPVCNACGLYYKLHQVNRPLTMRKD GIQTRNRKASGKGKKKRGSSLGGTGAAEGPAGGFMVVAGGSGSGNCGEVASGLTLGPPGT AHLYQGLGPVVLSGPVSHLMPFPGPLLGSPTGSFPTGPMPPTTSTTVVAPLSS |
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| The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes | |||||
| Cytokines / Cytokine receptors | [+] 2 Cytokines / Cytokine receptors Co-regulated By This TF | + | |||
| 1 | Erythropoietin Receptor (EPOR) | Successful Target | Target Info | [14] | |
| 2 | Interferon-gamma (IFNG) | Successful Target | Target Info | [15] | |
| Glycoproteins | [+] 1 Glycoproteins Co-regulated By This TF | + | |||
| 1 | von Willebrand factor (VWF) | Successful Target | Target Info | [2] | |
| Transcription factors | [+] 1 Transcription factors Co-regulated By This TF | + | |||
| 1 | Wilms tumor protein (WT1) | Clinical trial Target | Target Info | [13] | |
| TF Name | Octamer-binding protein 1 (POU2F1) | ||||
| Classification | Superclass | Helix-turn-helix | |||
| Class | Homeo domain | ||||
| Family | POU domain factors | ||||
| Regulation Type | Decrease | ||||
| Regulation Mechanism | Binding of the nuclear protein to theVWFAT-rich sequence in mobility shift assays is inhibited by competition with a consensusOct-1binding site and with a silencer octamer-like sequence from the vascular cell adhesion molecule-1 (VCAM-1)promoter.. | [3] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay, DNase I Footprint Analysis | [3] | |||
| UniProt ID | |||||
| Sequence |
MNNPSETSKPSMESGDGNTGTQTNGLDFQKQPVPVGGAISTAQAQAFLGHLHQVQLAGTS
LQAAAQSLNVQSKSNEESGDSQQPSQPSQQPSVQAAIPQTQLMLAGGQITGLTLTPAQQQ LLLQQAQAQAQLLAAAVQQHSASQQHSAAGATISASAATPMTQIPLSQPIQIAQDLQQLQ QLQQQNLNLQQFVLVHPTTNLQPAQFIISQTPQGQQGLLQAQNLLTQLPQQSQANLLQSQ PSITLTSQPATPTRTIAATPIQTLPQSQSTPKRIDTPSLEEPSDLEELEQFAKTFKQRRI KLGFTQGDVGLAMGKLYGNDFSQTTISRFEALNLSFKNMCKLKPLLEKWLNDAENLSSDS SLSSPSALNSPGIEGLSRRRKKRTSIETNIRVALEKSFLENQKPTSEEITMIADQLNMEK EVIRVWFCNRRQKEKRINPPSSGGTSSSPIKAIFPSPTSLVATTPSLVTSSAATTLTVSP VLPLTSAAVTNLSVTGTSDTTSNNTATVISTAPPASSAVTSPSLSPSPSASASTSEASSA SETSTTQTTSTPLSSPLGTSQVMVTASGLQTAAAAALQGAAQLPANASLAAMAAAAGLNP SLMAPSQFAAGGALLSLNPGTLSGALSPALMSNSTLATIQALASGGSLPITSLDATGNLV FANAGGAPNIVTAPLFLNPQNLSLLTSNPVSLVSAAAASAGNSAPVASLHATSTSAESIQ NSLFTVASASGAASTTTTASKAQ |
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| The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes | |||||
| Ester hydrolases | [+] 1 Ester hydrolases Co-regulated By This TF | + | |||
| 1 | Lipoprotein lipase (LPL) | Successful Target | Target Info | [16] | |
| G protein-coupled receptors | [+] 1 G protein-coupled receptors Co-regulated By This TF | + | |||
| 1 | Gonadotropin-releasing hormone receptor (GNRHR) | Successful Target | Target Info | [9] | |
| Glycoproteins | [+] 1 Glycoproteins Co-regulated By This TF | + | |||
| 1 | von Willebrand factor (VWF) | Successful Target | Target Info | [3] | |
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Ets transcription factors bind and transactivate the core promoter of the von Willebrand factor gene. Oncogene. 1997 Dec 18;15(25):3091-102. | ||||
| REF 2 | Endothelial-cell-specific regulation of von Willebrand factor gene expression. Mol Cell Biol. 1994 Feb;14(2):999-1008. | ||||
| REF 3 | Oct-1 is involved in the transcriptional repression of the von willebrand factor gene promoter. Blood. 1998 Aug 15;92(4):1247-58. | ||||
| REF 4 | A +220 GATA motif mediates basal but not endotoxin-repressible expression of the von Willebrand factor promoter in Hprt-targeted transgenic mice. J Thromb Haemost. 2009 Aug;7(8):1384-92. | ||||
| REF 5 | Pi 1 binding sites are negative regulators of bcl-2 expression in pre-B cells. Mol Cell Biol. 1995 Jul;15(7):3840-7. | ||||
| REF 6 | Identification and characterization of a novel Ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene prom... J Biol Chem. 1997 Apr 18;272(16):10389-95. | ||||
| REF 7 | Transcriptional regulation of endothelial nitric-oxide synthase by lysophosphatidylcholine. J Biol Chem. 1998 Jun 12;273(24):14885-90. | ||||
| REF 8 | 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 9 | Functional mapping of a placenta-specific upstream promoter for human gonadotropin-releasing hormone receptor gene. Endocrinology. 2001 Apr;142(4):1506-16. | ||||
| REF 10 | N(G)-monomethyl-L-arginine inhibits erythropoietin gene expression by stimulating GATA-2. Blood. 2000 Sep 1;96(5):1716-22. | ||||
| REF 11 | 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 12 | Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells. J Biol Chem. 1995 Jun 23;270(25):15320-6. | ||||
| REF 13 | Transactivation of an intronic hematopoietic-specific enhancer of the human Wilms' tumor 1 gene by GATA-1 and c-Myb. J Biol Chem. 1997 Nov 14;272(46):29272-80. | ||||
| REF 14 | Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs. Nucleic Acids Res. 1995 Aug 11;23(15):3041-9. | ||||
| REF 15 | Two essential regulatory elements in the human interferon gamma promoter confer activation specific expression in T cells. J Exp Med. 1993 Nov 1;178(5):1483-96. | ||||
| REF 16 | Transcriptional regulation of the human lipoprotein lipase gene in 3T3-L1 adipocytes. J Biol Chem. 1991 Oct 5;266(28):18958-63. | ||||
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