Target General Information
Target ID T03661 Target Info
Target Name Adenosine deaminase (ADA)
Synonyms Adenosine aminohydrolase; ADA1
Target Type Successful Target
Gene Name ADA
Biochemical Class Carbon-nitrogen hydrolase
UniProt ID
The Transcription Factors (TFs) Regulating This Target
TF Name c-Myb proto-oncogene (MYB)
Classification Superclass Helix-turn-helix
Class Tryptophan clusters
Family Myb
Subfamily Myb-factors
Regulation Type Increase
Regulation Mechanism Fetal murine thymus exhibited a striking concordance of endogenous c-myb expression with that of mouse ADA and human ADA LCR-directed transgene expression. Point mutation of the c-Myb site within the intact 2.3-kb LCR severely attenuated enhancer activity in transfections and LCR activity in transgenic thymocytes. Within the context of a complex enhancer and LCR, c-Myb can act as an organizer of thymocyte-specific gene expression via a single binding site. [1]
Evidence Score (E-score) 2 +
1 Chromatin Immunoprecipitation Assay [4]
2 Electrophoretic Mobility Shift Assay, Chloramphenicol Acetyltransferase Assay [1]
UniProt ID
Sequence
MARRPRHSIYSSDEDDEDFEMCDHDYDGLLPKSGKRHLGKTRWTREEDEKLKKLVEQNGT
DDWKVIANYLPNRTDVQCQHRWQKVLNPELIKGPWTKEEDQRVIELVQKYGPKRWSVIAK
HLKGRIGKQCRERWHNHLNPEVKKTSWTEEEDRIIYQAHKRLGNRWAEIAKLLPGRTDNA
IKNHWNSTMRRKVEQEGYLQESSKASQPAVATSFQKNSHLMGFAQAPPTAQLPATGQPTV
NNDYSYYHISEAQNVSSHVPYPVALHVNIVNVPQPAAAAIQRHYNDEDPEKEKRIKELEL
LLMSTENELKGQQVLPTQNHTCSYPGWHSTTIADHTRPHGDSAPVSCLGEHHSTPSLPAD
PGSLPEESASPARCMIVHQGTILDNVKNLLEFAETLQFIDSFLNTSSNHENSDLEMPSLT
STPLIGHKLTVTTPFHRDQTVKTQKENTVFRTPAIKRSILESSPRTPTPFKHALAAQEIK
YGPLKMLPQTPSHLVEDLQDVIKQESDESGIVAEFQENGPPLLKKIKQEVESPTDKSGNF
FCSHHWEGDSLNTQLFTQTSPVADAPNILTSSVLMAPASEDEDNVLKAFTVPKNRSLASP
LQPCSSTWEPASCGKMEEQMTSSSQARKYVNAFSARTLVM
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Carbon-nitrogen hydrolases [+] 1 Carbon-nitrogen hydrolases Co-regulated By This TF +
1 Adenosine deaminase (ADA) Successful Target Target Info [1]
Collagens [+] 1 Collagens Co-regulated By This TF +
1 Collagen I (COL1A2) Clinical trial Target Target Info [5]
TF Name Sp1 transcription factor (SP1)
Classification Superclass Zinc-coordinating DNA-binding domains
Class Cys2His2 zinc finger domain
Family Ubiquitous factors
Regulation Type Increase
Regulation Mechanism Examination of the promoter region of ADA by homology searches revealed six putative Sp1 binding sites. [2]
Evidence Score (E-score) 1 +
1 Chloramphenicol Acetyltransferase Assay, Electrophoretic Mobility Shift Assay, DNase I Footprint Analysis [2]
UniProt ID
Sequence
MSDQDHSMDEMTAVVKIEKGVGGNNGGNGNGGGAFSQARSSSTGSSSSTGGGGQESQPSP
LALLAATCSRIESPNENSNNSQGPSQSGGTGELDLTATQLSQGANGWQIISSSSGATPTS
KEQSGSSTNGSNGSESSKNRTVSGGQYVVAAAPNLQNQQVLTGLPGVMPNIQYQVIPQFQ
TVDGQQLQFAATGAQVQQDGSGQIQIIPGANQQIITNRGSGGNIIAAMPNLLQQAVPLQG
LANNVLSGQTQYVTNVPVALNGNITLLPVNSVSAATLTPSSQAVTISSSGSQESGSQPVT
SGTTISSASLVSSQASSSSFFTNANSYSTTTTTSNMGIMNFTTSGSSGTNSQGQTPQRVS
GLQGSDALNIQQNQTSGGSLQAGQQKEGEQNQQTQQQQILIQPQLVQGGQALQALQAAPL
SGQTFTTQAISQETLQNLQLQAVPNSGPIIIRTPTVGPNGQVSWQTLQLQNLQVQNPQAQ
TITLAPMQGVSLGQTSSSNTTLTPIASAASIPAGTVTVNAAQLSSMPGLQTINLSALGTS
GIQVHPIQGLPLAIANAPGDHGAQLGLHGAGGDGIHDDTAGGEEGENSPDAQPQAGRRTR
REACTCPYCKDSEGRGSGDPGKKKQHICHIQGCGKVYGKTSHLRAHLRWHTGERPFMCTW
SYCGKRFTRSDELQRHKRTHTGEKKFACPECPKRFMRSDHLSKHIKTHQNKKGGPGVALS
VGTLPLDSGAGSEGSGTATPSALITTNMVAMEAICPEGIARLANSGINVMQVADLQSINI
SGNGF
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Acyltransferases [+] 2 Acyltransferases Co-regulated By This TF +
1 Glutathione S-transferase P (GSTP1) Clinical trial Target Target Info [6]
2 Lecithin-cholesterol acyltransferase (LCAT) Clinical trial Target Target Info [7]
Apolipoproteins [+] 2 Apolipoproteins Co-regulated By This TF +
1 Apolipoprotein A-I (APOA1) Clinical trial Target Target Info [8]
2 Apolipoprotein E (APOE) Clinical trial Target Target Info [9]
Apoptosis regulators [+] 1 Apoptosis regulators Co-regulated By This TF +
1 Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) Clinical trial Target Target Info [10]
Carbon-nitrogen hydrolases [+] 1 Carbon-nitrogen hydrolases Co-regulated By This TF +
1 Adenosine deaminase (ADA) Successful Target Target Info [2]
Caveolin proteins [+] 1 Caveolin proteins Co-regulated By This TF +
1 Caveolin 1 (CAV1) Literature-reported Target Target Info [11]
Collagens [+] 1 Collagens Co-regulated By This TF +
1 Collagen I (COL1A2) Clinical trial Target Target Info [12]
Cytokines / Cytokine receptors [+] 2 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Erythropoietin Receptor (EPOR) Successful Target Target Info [13]
2 Interferon-gamma (IFNG) Successful Target Target Info [14]
Ester hydrolases [+] 2 Ester hydrolases Co-regulated By This TF +
1 Acetylcholinesterase (AChE) Successful Target Target Info [15]
2 M-phase inducer phosphatase 3 (MPIP3) Literature-reported Target Target Info [16]
G protein-coupled receptors [+] 3 G protein-coupled receptors Co-regulated By This TF +
1 5-HT 1A receptor (HTR1A) Successful Target Target Info [17]
2 C-X-C chemokine receptor type 4 (CXCR4) Successful Target Target Info [18]
3 Thromboxane A2 receptor (TBXA2R) Successful Target Target Info [19]
Glycoproteins [+] 2 Glycoproteins Co-regulated By This TF +
1 Cholesteryl ester transfer protein (CETP) Clinical trial Target Target Info [20]
2 Tracheobronchial mucin 5A (MUC5AC) Literature-reported Target Target Info [21]
Growth factors [+] 4 Growth factors Co-regulated By This TF +
1 Platelet-derived growth factor A (PDGFA) Clinical trial Target Target Info [22]
2 Platelet-derived growth factor B (PDGFB) Clinical trial Target Target Info [23]
3 Thrombomodulin (THBD) Discontinued Target Target Info [24]
4 Transforming growth factor beta 1 (TGFB1) Successful Target Target Info [25]
Immunoglobulins [+] 1 Immunoglobulins Co-regulated By This TF +
1 Intercellular adhesion molecule ICAM-1 (ICAM1) Successful Target Target Info [26]
Integrins [+] 1 Integrins Co-regulated By This TF +
1 Integrin alpha-2 (ITGA2) Clinical trial Target Target Info [27]
Kinases [+] 5 Kinases Co-regulated By This TF +
1 Casein kinase II alpha (CSNK2A1) Clinical trial Target Target Info [28]
2 Epidermal growth factor receptor (EGFR) Successful Target Target Info [29]
3 Serine/threonine-protein kinase pim-1 (PIM1) Clinical trial Target Target Info [30]
4 Telomerase reverse transcriptase (TERT) Clinical trial Target Target Info [31]
5 Thymidine kinase 1 (TK1) Successful Target Target Info [32]
Lipoprotein receptors [+] 1 Lipoprotein receptors Co-regulated By This TF +
1 Low-density lipoprotein receptor (LDL-R) Successful Target Target Info [33]
Lyases [+] 2 Lyases Co-regulated By This TF +
1 Histidine decarboxylase (HDC) Clinical trial Target Target Info [34]
2 Leukotriene C4 synthase (LTC4S) Patented-recorded Target Target Info [35]
Nuclear hormone receptors [+] 2 Nuclear hormone receptors Co-regulated By This TF +
1 Hepatocyte nuclear factor 4-alpha (HNF4A) Literature-reported Target Target Info [36]
2 Progesterone receptor (PGR) Successful Target Target Info [37]
Oxidoreductases [+] 9 Oxidoreductases Co-regulated By This TF +
1 Arachidonate 12-lipoxygenase (12-LOX) Literature-reported Target Target Info [38]
2 Bacterial Triosephosphate isomerase (Bact TPI) Literature-reported Target Target Info [39]
3 Catalase (CAT) Clinical trial Target Target Info [40]
4 Cholesterol desmolase (CYP11A1) Successful Target Target Info [41]
5 Dopamine beta hydroxylase (DBH) Clinical trial Target Target Info [42]
6 Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1) Clinical trial Target Target Info [43]
7 Heme oxygenase 1 (HMOX1) Clinical trial Target Target Info [44]
8 Nitric-oxide synthase endothelial (NOS3) Clinical trial Target Target Info [45]
9 Superoxide dismutase Cu-Zn (SOD Cu-Zn) Clinical trial Target Target Info [46]
Peptidases [+] 4 Peptidases Co-regulated By This TF +
1 Caspase-8 (CASP8) Patented-recorded Target Target Info [47]
2 Cathepsin D (CTSD) Clinical trial Target Target Info [48]
3 Dibasic-processing enzyme (Furin) Patented-recorded Target Target Info [49]
4 Neutral endopeptidase (MME) Clinical trial Target Target Info [50]
Pro-neuropeptides [+] 1 Pro-neuropeptides Co-regulated By This TF +
1 Neuropeptide Y (NPY) Literature-reported Target Target Info [51]
Small GTPases [+] 1 Small GTPases Co-regulated By This TF +
1 GTPase HRas (HRAS) Literature-reported Target Target Info [52]
Somatotropin / Prolactins [+] 1 Somatotropin / Prolactins Co-regulated By This TF +
1 Somatotropin (GH1) Clinical trial Target Target Info [53]
Transcription factors [+] 2 Transcription factors Co-regulated By This TF +
1 Transcription factor Sp1 (SP1) Clinical trial Target Target Info [54]
2 Wilms tumor protein (WT1) Clinical trial Target Target Info [55]
Transferrins [+] 1 Transferrins Co-regulated By This TF +
1 Transferrin (TF) Clinical trial Target Target Info [56]
Zinc-fingers [+] 1 Zinc-fingers Co-regulated By This TF +
1 Utrophin (UTRN) Clinical trial Target Target Info [57]
TF Name Lymphoid enhancer-binding factor 1 (LEF1)
Classification Superclass beta-Scaffold Factors with Minor Groove Contacts
Class HMG
Family TCF-1
Regulation Mechanism DpnII accessibility experiments indicated dramatic changes in the chromatin organization of theADAenhancerin transgenic mice with a mutatedLEF1/TCF1 site. [3]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay, DNase I Footprint Analysis [3]
UniProt ID
Sequence
MPQLSGGGGGGGGDPELCATDEMIPFKDEGDPQKEKIFAEISHPEEEGDLADIKSSLVNE
SEIIPASNGHEVARQAQTSQEPYHDKAREHPDDGKHPDGGLYNKGPSYSSYSGYIMMPNM
NNDPYMSNGSLSPPIPRTSNKVPVVQPSHAVHPLTPLITYSDEHFSPGSHPSHIPSDVNS
KQGMSRHPPAPDIPTFYPLSPGGVGQITPPLGWQGQPVYPITGGFRQPYPSSLSVDTSMS
RFSHHMIPGPPGPHTTGIPHPAIVTPQVKQEHPHTDSDLMHVKPQHEQRKEQEPKRPHIK
KPLNAFMLYMKEMRANVVAECTLKESAAINQILGRRWHALSREEQAKYYELARKERQLHM
QLYPGWSARDNYGKKKKRKREKLQESASGTGPRMTAAYI
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Carbon-nitrogen hydrolases [+] 1 Carbon-nitrogen hydrolases Co-regulated By This TF +
1 Adenosine deaminase (ADA) Successful Target Target Info [3]
References
REF 1 A central role for a single c-Myb binding site in a thymic locus control region. Mol Cell Biol. 1995 Oct;15(10):5707-15.
REF 2 Sp1 is essential for both enhancer-mediated and basal activation of the TATA-less human adenosine deaminase promoter. Nucleic Acids Res. 1994 Feb 25;22(4):669-77.
REF 3 An enhancer LEF-1/TCF-1 site is essential for insertion site-independent transgene expression in thymus. Nucleic Acids Res. 1996 Dec 15;24(24):5034-44.
REF 4 Revisiting a selection of target genes for the hematopoietic transcription factor c-Myb using chromatin immunoprecipitation and c-Myb knockdown. Blood Cells Mol Dis. 2007 Nov-Dec;39(3):278-86.
REF 5 Characterization of the c-Myb-responsive region and regulation of the human type I collagen alpha 2 chain gene by c-Myb. J Biol Chem. 2003 Jan 17;278(3):1533-41.
REF 6 Sp1-mediated transcriptional activation of the human Pi class glutathione S-transferase promoter. J Biol Chem. 1996 Jan 12;271(2):1054-60.
REF 7 Binding and functional effects of transcription factors Sp1 and Sp3 on the proximal human lecithin:cholesterol acyltransferase promoter. J Lipid Res. 1998 May;39(5):969-77.
REF 8 Involvement of early growth response factor Egr-1 in apolipoprotein AI gene transcription. J Biol Chem. 1995 Mar 24;270(12):7004-10.
REF 9 Characterization of a human apolipoprotein E gene enhancer element and its associated protein factors. J Biol Chem. 1990 Jun 5;265(16):9496-504.
REF 10 Regulation of MCL1 through a serum response factor/Elk-1-mediated mechanism links expression of a viability-promoting member of the BCL2 family to the induction of hematopoietic cell differentiation. J Biol Chem. 1999 Jan 15;274(3):1801-13.
REF 11 Intracellular cholesterol transport in synchronized human skin fibroblasts. Biochemistry. 1999 Feb 23;38(8):2506-13.
REF 12 Transforming growth factor-beta stimulates alpha 2(I) collagen gene expression through a cis-acting element that contains an Sp1-binding site. J Biol Chem. 1994 May 20;269(20):14828-34.
REF 13 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 14 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 15 Transcription factor repression and activation of the human acetylcholinesterase gene. J Biol Chem. 1995 Oct 6;270(40):23511-9.
REF 16 Cell cycle regulation of cdc25C transcription is mediated by the periodic repression of the glutamine-rich activators NF-Y and Sp1. Nucleic Acids Res. 1995 Oct 11;23(19):3822-30.
REF 17 The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1. J Biol Chem. 1996 Feb 23;271(8):4417-30.
REF 18 Genomic organization and functional characterization of the chemokine receptor CXCR4, a major entry co-receptor for human immunodeficiency virus type 1. J Biol Chem. 1998 Feb 20;273(8):4754-60.
REF 19 Novel role for Sp1 in phorbol ester enhancement of human platelet thromboxane receptor gene expression. J Biol Chem. 1996 Aug 16;271(33):19696-704.
REF 20 Transcriptional regulation of the cholesteryl ester transfer protein gene by the orphan nuclear hormone receptor apolipoprotein AI regulatory protein-1. J Biol Chem. 1995 Dec 15;270(50):29916-22.
REF 21 The human uncoupling protein-3 gene promoter requires MyoD and is induced by retinoic acid in muscle cells. FASEB J. 2000 Nov;14(14):2141-3.
REF 22 The Wilms' tumor gene product, WT1, represses transcription of the platelet-derived growth factor A-chain gene. J Biol Chem. 1992 Nov 5;267(31):21999-2002.
REF 23 Identification of a thrombin response element in the human platelet-derived growth factor B-chain (c-sis) promoter. J Biol Chem. 1996 Feb 9;271(6):3025-32.
REF 24 Acceleration of thrombomodulin gene transcription by retinoic acid: retinoic acid receptors and Sp1 regulate the promoter activity through interactions with two different sequences in the 5'-flanking region of human gene. J Biol Chem. 2001 Jan 26;276(4):2440-50.
REF 25 Regulation of the transforming growth factor-beta 1 and -beta 3 promoters by transcription factor Sp1. Gene. 1993 Jul 30;129(2):223-8.
REF 26 Stat1 depends on transcriptional synergy with Sp1. J Biol Chem. 1995 Dec 22;270(51):30264-7.
REF 27 Binding of phosphorylated Sp1 protein to tandem Sp1 binding sites regulates alpha2 integrin gene core promoter activity. Blood. 1997 Jul 15;90(2):678-89.
REF 28 Transcription factors ets1, NF-kappa B, and Sp1 are major determinants of the promoter activity of the human protein kinase CK2alpha gene. J Biol Chem. 2000 Jun 16;275(24):18327-36.
REF 29 Identification of an estrogen-mediated deoxyribonucleic acid-binding independent transactivation pathway on the epidermal growth factor receptor gene promoter. Endocrinology. 2000 Jun;141(6):2266-74.
REF 30 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 31 Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res. 2000 Feb 1;28(3):669-77.
REF 32 Constitutive protection of E2F recognition sequences in the human thymidine kinase promoter during cell cycle progression. J Biol Chem. 1997 Nov 28;272(48):30483-90.
REF 33 Co-stimulation of promoter for low density lipoprotein receptor gene by sterol regulatory element-binding protein and Sp1 is specifically disrupted by the yin yang 1 protein. J Biol Chem. 1999 May 7;274(19):13025-32.
REF 34 Mast cell-/basophil-specific transcriptional regulation of human L-histidine decarboxylase gene by CpG methylation in the promoter region. J Biol Chem. 1998 Nov 20;273(47):31607-14.
REF 35 Cell-specific transcription of leukotriene C(4) synthase involves a Kruppel-like transcription factor and Sp1. J Biol Chem. 2000 Mar 24;275(12):8903-10.
REF 36 Regulatory mechanisms controlling human hepatocyte nuclear factor 4alpha gene expression. Mol Cell Biol. 2001 Nov;21(21):7320-30.
REF 37 Sp1 binding sites and an estrogen response element half-site are involved in regulation of the human progesterone receptor A promoter. Mol Endocrinol. 2000 Jul;14(7):972-85.
REF 38 Transcriptional activation of human 12-lipoxygenase gene promoter is mediated through Sp1 consensus sites in A431 cells. Biochem J. 1997 May 15;324 ( Pt 1):133-40.
REF 39 Minimal sequence and factor requirements for the initiation of transcription from an atypical, TATATAA box-containing housekeeping promoter. J Biol Chem. 1990 Nov 25;265(33):20524-32.
REF 40 Regulation of the catalase gene promoter by Sp1, CCAAT-recognizing factors, and a WT1/Egr-related factor in hydrogen peroxide-resistant HP100 cells. Cancer Res. 2001 Aug 1;61(15):5885-94.
REF 41 Actions of two different cAMP-responsive sequences and an enhancer of the human CYP11A1 (P450scc) gene in adrenal Y1 and placental JEG-3 cells. J Biol Chem. 1994 Mar 4;269(9):6362-9.
REF 42 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 43 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 44 Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line. Biochem J. 2002 Nov 1;367(Pt 3):641-52.
REF 45 Transcriptional regulation of endothelial nitric-oxide synthase by lysophosphatidylcholine. J Biol Chem. 1998 Jun 12;273(24):14885-90.
REF 46 Sp1 and C/EBP-related factor regulate the transcription of human Cu/Zn SOD gene. Gene. 1996 Oct 31;178(1-2):177-85.
REF 47 The human caspase-8 promoter sustains basal activity through SP1 and ETS-like transcription factors and can be up-regulated by a p53-dependent mechanism. J Biol Chem. 2003 Jul 25;278(30):27593-604.
REF 48 Estrogen receptor-Sp1 complexes mediate estrogen-induced cathepsin D gene expression in MCF-7 human breast cancer cells. J Biol Chem. 1994 Jun 3;269(22):15912-7.
REF 49 Expression of the dibasic proprotein processing enzyme furin is directed by multiple promoters. J Biol Chem. 1994 Mar 25;269(12):9298-303.
REF 50 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 51 Transcriptional regulation of the human neuropeptide Y gene by nerve growth factor. J Biol Chem. 1994 Jun 3;269(22):15460-8.
REF 52 Effect of abasic linker substitution on triplex formation, Sp1 binding, and specificity in an oligonucleotide targeted to the human Ha-ras promoter. Nucleic Acids Res. 1994 May 25;22(10):1909-16.
REF 53 Sp1 and thyroid hormone receptor differentially activate expression of human growth hormone and chorionic somatomammotropin genes. J Biol Chem. 1991 May 25;266(15):9805-13.
REF 54 Cloning and characterization of the 5'-flanking region of the human transcription factor Sp1 gene. J Biol Chem. 2001 Jun 22;276(25):22126-32.
REF 55 Characterization of the transcriptional regulatory region of the human WT1 gene. Oncogene. 1993 Nov;8(11):3123-32.
REF 56 YY1 and Sp1 transcription factors bind the human transferrin gene in an age-related manner. J Gerontol A Biol Sci Med Sci. 1996 Jan;51(1):B66-75.
REF 57 Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter. J Mol Biol. 2001 Mar 9;306(5):985-96.

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